Scientists grow human mini-lungs as animal alternative for nanomaterial safety testing – The University of Manchester

Using the same biological endpoints, the teams human lung organoids showed a similar biological response, which validates them as tools for predicting nanomaterial driven responses in lung tissue.

The human organoids enabled better understanding of interactions of nanomaterials with the model tissue, but at the cellular level.

Graphene oxide (GO), a flat, thin and flexible form of carbon nanomaterial, was found to be momentarily trapped out of harms way in a substance produced by the respiratory system called secretory mucin.

In contrast, MWCNT induced a more persistent interaction with the alveolar cells, with more limited mucin secretion and leading to the growth of fibrous tissue.

In a further development, Dr Issa and Vranic based at the Universitys Centre for Nanotechnology in Medicine are now developing and studying a ground-breaking human lung organoid that also contains an integrated immune cell component.

Dr Vranic said: With further validation, prolonged exposure, and the incorporation of an immune component, human lung organoids could greatly reduce the need for animals used in nanotoxicology research.

Developed to encourage humane animal research, the 3Rs of replacement, reduction and refinement are now embedded in UK law and in many other countries.

Public attitudes consistently show that support for animal research is conditional on the 3Rs being put into practice.

Professor Kostas Kostarelos, Chair of Nanomedicine at the University said: Current 2D testing of nanomaterials using two-dimensional cell culture models provide some understanding of cellular effects, but they are so simplistic as it can only partially depict the complex way cells communicate with each other.

It certainly does not represent the complexity of the human pulmonary epithelium and may misrepresent the toxic potential of nanomaterials, for better or for worse.

Though animals will still be needed in research for the foreseeable future, 3D organoids nevertheless are an exciting prospect in our research field and in research more generally as a human equivalent and animal alternative.

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Scientists grow human mini-lungs as animal alternative for nanomaterial safety testing - The University of Manchester

New micromaterial to fight cancer with nanoparticle-targeting – healthcare-in-europe.com

In the clinical context, the use of these materials in the treatment of colorectal cancer should largely enhance drug efficiency and patients comfort, while at the same time minimizing undesired side effects

The new micromaterials developed by researchers are formed by chains of amino acids known as polypeptides, which are functional and bioavailable in the form of nanoparticles that can be released and targeted to specific types of cancer cells, for selective destruction.

The research team analyzed the molecular structure of these materials and the dynamics behind the secretion process, both in vitro and in vivo. In an animal model of CXCR4+ colorectal cancer, the system showed high performance upon subcutaneous administration, and how the released protein nanoparticles accumulated in tumor tissues. It is important to highlight that this accumulation is more efficient than when the protein is administered in blood. This fact offers an unexpected new way to ensure high local drug levels and better clinical efficacy, thus avoiding repeated intravenous administration regimens, explains Professor Antonio Villaverde. "In the clinical context, the use of these materials in the treatment of colorectal cancer should largely enhance drug efficiency and patients comfort, while at the same time minimizing undesired side effects."

Source:Universitat Autnoma de Barcelona

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New micromaterial to fight cancer with nanoparticle-targeting - healthcare-in-europe.com

Nanomedicine Market Size Expected to Reach USD 562.93 Bn by 2032 – GlobeNewswire

Ottawa, April 03, 2024 (GLOBE NEWSWIRE) -- The global nanomedicine market size was valued at USD 219.34 billion in 2023 and is predicted to hit around USD 494.62 billion by 2031, a study published by Towards Healthcare a sister firm of Precedence Research.

Report Highlights:

According to recent data, around 100+ nanomedicines have been commercially marketed, with almost 550+ nanomedicines under clinical trials.

Nanomedicine involves creating and utilizing tiny structures or devices, typically between 1 and 100 nanometers in size, for medical purposes such as diagnosis and treatment. These nanoscale objects or tools, including nano-robots, skin patches, or other nanostructured materials, leverage their unique properties to achieve specific medical effects.

In medicine, nanomedicine holds promise for better drug delivery systems, more accurate imaging techniques, and even tiny devices that can target and treat diseases directly at the cellular level. Electronics enables the development of smaller and faster devices, leading to better computers, smartphones, and other gadgets.

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Nanomedicine also has applications in energy, where it can improve the efficiency of solar panels and batteries and environmental protection, with nanomaterials being used to clean up pollutants. Nanomedicine has the potential to revolutionize many aspects of our lives, from healthcare and electronics to energy and the environment, making it a crucial area of research and innovation.

Nanomedicine is increasingly used to treat a wide range of diseases due to its ability to target specific cells or tissues precisely. In cancer treatment, nanomedicine delivers chemotherapy drugs directly to cancer cells, reducing side effects and improving effectiveness. It's also used in imaging techniques like MRI and CT scans to detect tumors early.

Additionally, nanomedicine is being explored for treating neurological disorders such as Alzheimer's and Parkinson's by delivering drugs across the blood-brain barrier and targeting diseased cells. In infectious diseases like HIV/AIDS and tuberculosis, nanomedicine can enhance drug delivery and improve the efficacy of antiviral or antibiotic medications. Furthermore, nanomedicine is being investigated for treating cardiovascular diseases, diabetes, and autoimmune disorders by developing targeted drug delivery systems and implants that regulate blood sugar levels or modulate immune responses.

Nanomedicine holds great promise in revolutionizing the treatment of various diseases by providing more effective, targeted, and less invasive therapies, potentially improving patient outcomes and quality of life.

Cancer Rates Are on the Rise

In 2022, there were about 1.92 million new cancer cases in the United States, and around 609,360 people died from cancer. Globally, this adds up to 9.6 million lives lost. Because cancer is becoming more common, we need new and better treatments. Nanomedicine is one promising way to fight cancer. It works by delivering treatments directly to cancer cells, which can make them more effective and cause fewer side effects. As more people get cancer around the world, scientists are seeing how nanomedicine could change the way we treat it. By using minimal materials and methods, researchers hope to improve cancer treatments and ease the disease's burden on society.

The rising number of individuals with cancer has led to significant growth in the nanomedicine market. This is because nanomedicine has some cool ways to help treat cancer. It helps deliver cancer drugs to the cancer cells so they work better and have fewer side effects. It improves how we see cancer using fancy imaging techniques like MRI and CT scans. This helps doctors find cancer early and treat it sooner.

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Biomarker Detection

Biomarker detection using nanomedicine is a fancy way of saying that tiny devices and sensors can find signs of cancer in our body fluids, like blood or urine. These signs, called biomarkers, indicate whether cancer is present. These nanomedicine-based devices are super sensitive and accurate to spot even tiny amounts of these biomarkers. This helps doctors find cancer early when it's easier to treat and has a better chance of being cured.

Biomarker Detection Device for Diagnosis of Cancer

Imaging Probes:

AI-Powered Nanoparticle Bio-Detection Platform:

Not only can these nanodevices detect cancer, but they can also keep an eye on how the disease is changing over time. This helps doctors track treatment progress and see if it's working well. Plus, by predicting how cancer might respond to different treatments, these nanomedicine-based tools can help personalize treatment plans for each patient. Biomarker detection using nanomedicine is a powerful tool for early cancer detection, monitoring disease progression, and guiding treatment decisions, all of which can improve outcomes for cancer patients.

Nanomedicine lets us make personalized treatments for each person's unique cancer. That means better results and fewer problems from treatment. It helps develop new cancer therapies like heat and light therapy and boosts the body's immune system to fight cancer. Nanomedicine can spot tiny signs of cancer in our body fluids, which helps catch it early and track how it's doing during treatment. So, because more people have cancer, there's a more significant need for these intelligent nanomedicine solutions to help diagnose, treat, and keep an eye on cancer, which is making the nanomedicine market grow.

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Nanomedicines Offer Promising Advantages for Dealing with Alzheimer's

Alzheimer's disease ranked as the sixth most common cause of death in the United States, and it dropped to seventh place in both 2020 and 2021. Neurological disorders like Alzheimer's disease are becoming more common, and nanomedicine offers promising ways to manage them. In Alzheimer's, for example, the brain gets clogged with clumps of proteins, leading to memory loss and cognitive decline. Nanomedicine can help by delivering drugs directly to these protein clumps, breaking them apart and slowing down the progression of the disease.

For instance,

Additionally, nanoparticles can carry drugs across the blood-brain barrier, a protective layer around the brain that usually prevents medications from getting in. This allows for more effective treatment of neurological disorders.

Nanomedicine also enables the development of advanced imaging techniques to detect brain changes associated with neurological diseases early, allowing for timely intervention and treatment. Nanomaterials can create implants or devices that stimulate or regulate brain activity, relieving symptoms and improving the quality of life for patients with neurological disorders.

Furthermore, researchers are exploring using nanotechnology in regenerative medicine to repair damaged nerve cells and promote brain tissue regeneration. By harnessing the unique properties of nanomaterials, scientists are optimistic about the potential of nanotechnology to revolutionize the management of neurological disorders like Alzheimer's, offering hope for improved outcomes and quality of life for patients and their families.

More People Need Nanomedicine Worldwide as a Result of Advancements in Technology and Innovation

Continuous improvements in making tiny things, studying them, and simulating their behavior are pushing nanotechnology forward and making the market grow. Nanofabrication techniques are methods for building small structures, like using special machines to create tiny devices or materials. Characterization tools help us understand what these little things are made of and how they work by analyzing their properties. Simulation software allows scientists to predict how nanomaterials will behave under different conditions without physically testing them.

For instance,

All these advancements are opening up new possibilities for nanomedicine, making creating innovative products and solutions easier. For example, better nanofabrication techniques allow us to make smaller, more precise devices, while improved characterization tools help us understand how nanomaterials interact with living cells or the environment. This helps researchers develop new nanotechnology-based products for various industries, from electronics and healthcare to energy and environmental sustainability. As a result, the nanotechnology market is growing as more companies invest in developing and commercializing these advanced technologies.

Obtaining Approval for Nanomedicine Products Can Be Challenging

Getting approval for nanomedicine products can be tricky because nanoparticles behave differently than regular medicines. This makes it hard for regulators to determine their safety and effectiveness. To make things easier, we need to set up standard ways to test nanomedicine and transparent rules for how they should be regulated. This would help speed up the approval process and make it easier for these products to enter the market. Without these guidelines, it's tough for companies to get their nanomedicine products approved, which slows progress and makes it harder for patients to access these innovative treatments. Setting up clear rules and testing methods for nanomedicine is essential for getting these products out to those needing them.

A Few of the Worldwide Commercialized and FDA/EMA-Approved Formulations Based on Nanomedicines

Geographical Landscape

North America, including the United States, Canada, and Mexico, plays a significant role in nanomedicine. In the United States, many research institutions and companies work on nanomedicine. Major pharmaceutical companies invest much in nanotechnology for medicines, diagnostics, and treatments. The FDA makes sure nanomedicine products are safe and work well. Canada also does a lot of nanomedicine research. Universities, government, and companies work together on new ideas. Canadian companies focus on using nanotechnology to deliver drugs and make better medical images.

Rules in Canada make sure nanomedicine is developed and used responsibly. The North American nanomedicine market is growing because of solid funding, rules, and healthcare. More people have long-term illnesses, so there's a more significant need for new treatments. Better technology, like new ways to deliver drugs and diagnose diseases, is also helping. When academics, businesses, and government work together, it improves nanomedicine and helps it grow in North America.

Countries like China, Japan, India, and South Korea are big players in nanomedicine in the Asia-Pacific region.

For instance,

This conference aimed to share scientific advancements, industry developments, technical progress, and emerging challenges within the field of nanotechnology. They have many research centers and companies developing new nanomedicine products. Governments support these efforts with funding and initiatives. With growing healthcare needs and investments, the region is seeing rapid advancements in nanotechnology for medicine. Collaboration between countries is also helping to drive innovation and improve healthcare options.

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Competitive Landscape

The nanomedicine market is competitive, driven by innovation, research efforts, and market demand. Big pharma, startups, and research institutions vie to develop new nanomedicines, focusing on safety, efficacy, and manufacturing. Regulatory standards shape the landscape, favoring companies that navigate them well. Partnerships and mergers bolster positions, aiding in technology access and market expansion. It's a dynamic arena marked by innovation, regulatory compliance, and collaboration, all aimed at tackling healthcare needs with advanced nanotechnology solutions.

Recent Developments

Market Key Players

Market Segmentation

By Application

By Indication

By Molecule Type

By Geography

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Nanomedicine Market Size Expected to Reach USD 562.93 Bn by 2032 - GlobeNewswire

Histopathological biomarkers for predicting the tumour accumulation of nanomedicines – Nature.com

Quantification of the accumulation of nanomedicine in tumours

We first determined nanomedicine tumour accumulation in three mouse models with differing degrees of vascularization, stroma composition and target-site localization (Fig. 1a). The tumour models were A431 human epidermoid carcinoma, MLS human ovarian carcinoma and CT26 murine colon cancer. As a nanocarrier, we employed a 67kDa-sized poly(N-(2-hydroxypropyl) methacrylamide) (PHPMA) polymer, as this prototypic albumin-sized macromolecule has consistently provided us with high levels of tumour accumulation in a variety of models15,16,17. We used fluorescence reflectance imaging (FRI) and hybrid CTFMT to visualize and quantify the biodistribution and tumour accumulation of DY750-labelled PHPMA (Fig. 1b,c and Supplementary Fig. 1). When normalized to average tumour volume at the timepoint of analysis (250 mm3), at 72h post intravenous (i.v.) injection, we found average levels of target-site localization of 5.01.7, 8.51.6 and 10.21.7 percent of the injected dose (%ID) for A431, MLS and CT26 tumours, respectively, exemplifying sustained localization to tumours over time, as well as different accumulation patterns in the three models (P=0.0024, one-way analysis of variance (ANOVA); Fig. 1d and Supplementary Fig. 1). The tumours were then excised, and DY750-labelled PHPMA accumulation patterns were validated ex vivo using FRI (Supplementary Fig. 2). The collected tumours were fixed, sectioned and stained for biomarker assessment.

a, A schematic of the experimental protocol aimed at identifying tumour-tissue biomarkers that correlate with nanomedicine accumulation in tumours. The tumour accumulation of the prototypic polymeric nanocarrier, PHPMA, was assessed using CTFMT in three distinct mouse models with varying degrees of tumour targeting. Subsequently, correlation analyses were conducted using 23 tumour-tissue microenvironment features associated with tumour-targeted drug delivery, focusing on aspects related to the vasculature (red), stroma (green), macrophages (blue) and cellular density (grey). The dashed lines indicate double stained features. For further details, please refer to Supplementary Table 1. The illustration was created with BioRender.com. b, FRI-based, longitudinal optical imaging of DY750-labelled PHPMA accumulation in the tumours of mice with A431, MLS and CT26 tumours representing low, medium and high levels of target-site accumulation, respectively (the white dashed circles indicate tumour location, and one mouse per tumour model is shown). c,d, Longitudinal CTFMT visualization (c) and quantification of DY750-labelled PHPMA tumour accumulation (d) in percent of the injected dose (100% is equal to 2nmol of dye) normalized to 250mm tumour volume. The statistical significance between the two models was assessed via individual Students t-tests (A431 versus MLS, *P=0.0168; A431 versus CT26, **P=0.0025) and between all models via one-way ANOVA (#P=0.0024). Each data point represents a CTFMT scan of one animal.

We analysed 23 tumour microenvironment features associated with tumour-targeted drug delivery (Supplementary Table 1). These included vascular features, such as vessel density (CD31), perfusion (lectin) and angiogenesis (VEGFR2); lymph vessels (LYVE-1); extracellular matrix components, such as SMA, collagen I and collagen IV; tumour-associated macrophages (TAM; F4/80); and tumour cell density (4,6-diamidino-2-phenylindole). In addition, we analysed combinations of the above, via immunofluorescent double-stainings, to, for example, assess vessel support (SMA+/CD31+), vessel function (lectin+/CD31+) and the fraction of angiogenic vessels (VEGFR2+/CD31+).

The tumour-tissue biomarkers were captured and quantified via fluorescence microscopy and correlated with nanocarrier accumulation in A431, MLS and CT26 tumours (Fig. 2). Regarding blood vessel density and perfusion, we observed an overall good agreement between the number of (perfused) vessels and DY750-labelled PHPMA accumulation. The CT26 tumours had the highest number of total and functional blood vessels (89.035.9 and 48.018.8, respectively; Fig. 2a,b,g,h), and this was in line with their high level of polymer accumulation (10.21.7%ID per 250mm3; Fig. 1d). Conversely, A431 tumours had low levels of total and functional blood vessels (28.515.1 and 25.615.5, repectively; Fig. 2a,b,g,h), aligning with their low accumulation of DY750-labelled PHPMA (5.01.7%ID per 250mm3; Fig. 1d). Interestingly, while CT26 tumours had the highest absolute numbers of total and functional blood vessels, A431 tumours presented with the highest relative level of perfused vessels (91.3%, as compared with 62.7% for MLS and 54.9% for CT26; Supplementary Fig. 3j). This indicates that the absolute number of (functional) blood vessels is a more important factor determining nanomedicine tumour targeting than the relative fraction of vascular perfusion. In good agreement with this, also the absolute numbers of SMA+, Col I+, Col IV+ and VEGFR2+ blood vessels (Fig. 2c,d,i,j) correlated better with DY750-labelled PHPMA tumour accumulation than the relative fractions of SMA+, Col I+, Col IV+ and VEGFR2+ vessels (Supplementary Fig. 3jn).

af, Immunofluorescence stainings for all blood vessels (CD31) (a), actively perfused vessels (lectin) (b), pericyte-supported vessels (SMA) (c), angiogenic vessels (VEGFR2) (d), lymphatic vessels (LYVE-1) (e) and TAM (F4/80) (f) in A431, MLS and CT26 tumours. Scale bar, 50m. gl, Quantification of the immunofluorescence images for CD31+ vessels (g), lectin+ vessels (h), SMA+ vessels (i), VEGFR2+ vessels (j), LYVE-1+ vessels (k) and F4/80 (l) (no., number). The black bars indicate means. *P<0.05, **P<0.01 (Students t-test). Note that the analysis in gi is based on 10 magnification images, while the analysis in jl is based on 20 magnification. mr, Correlation of PHPMA tumour accumulation at 72h post injection (in percent of the injected dose (100% represents 2nmol of dye) normalized to 250mm tumour volume) with the respective tumour-tissue biomarker features (CD31+ vessels (m), lectin+ vessels (n), SMA+ vessels (o), VEGFR2+ vessels (p), LYVE-1+ vessels (q) and F4/80 (r)). The trendlines are shown per tumour model (colour-coded) and for all tumours together (black). The R2 values indicate the coefficient of determination and reflect the goodness of fit. Each data point represents one animal.

Regarding the retention component of nanomedicine tumour targeting, we particularly looked at LYVE-1+ lymphatic vessels and F4/80+ TAM. Interestingly, we observed that the tumour model with the highest level of PHPMA accumulation, that is, CT26, had almost double the number of LYVE-1+ lymphatic vessels as A431 and MLS (Fig. 2e,k). This indicates that the absence of effective lymphatics as a mediator of nanomedicine retention in tumours may be less important than originally anticipated18. It actually even suggests the opposite, which is that a certain degree of functional lymphatics in tumours may be needed to assist in attenuating the high interstitial fluid pressure that is typical of tumours19. A very good correlation was found between the density of TAM and nanomedicine accumulation (Fig. 2f,l,r). The area fraction of TAM increased from 2.2% to 5.1% to 7.7% for A431, MLS and CT26 tumours, respectively, correlating almost linearly with the increased tumour accumulation in these models (Fig. 1d) and resulting in good R2 values both within and across the three models (Fig. 2r). This finding corroborates an increasing number of notions that TAM act as a key reservoir for nanomedicine retention in tumours8,20. It furthermore implies that TAM density seems to be a suitable tumour-tissue biomarker to predict nanomedicine tumour accumulation.

Feature importance was assessed using gradient tree boosting (GTB). GTB is a machine learning technique for building predictive regression models based on a set of yes/no decision trees21,22,23. The trained GTB model considered all 23 features analysed as a regression model and was applied to predict polymeric nanomedicine tumour accumulation (Fig. 3a). Given the relatively small dataset, the leave-one-out method was employed to avoid the mixing of training and testing datasets. Ten decision trees, with a depth of up to eight questions, were found to be able to properly predict nanocarrier tumour accumulation based on histopathological features (R=0.70; Fig. 3b). As exemplified in Fig. 3c, GTB-based importance assessment identified the percentage of lectin+ (that is, functional vessels percentage) and angiogenic (that is, VEGFR2 vessels percentage) blood vessels, the density of TAM (that is, F4/80 area fraction (AF)) and the total, SMA+ and Col I+ number of blood vessels (that is, CD31 number, SMA number and Col I vessels number, respectively) as predictive features.

a, Schematic workflow. Tumour-tissue biomarkers were stained, quantified and correlated with the tumour accumulation of PHPMA nanocarriers. GTB-based machine learning was employed to rank feature importance using predicted versus measured PHPMA tumour accumulation values (Y, yes; N, no; B14, biomarker 14). b, N-fold cross-validation of predicted versus measured PHPMA tumour accumulation patterns illustrates the accuracy of the employed GTB method for predicting nanomedicine tumour targeting (in percent of the injected dose (100% represents 2nmol of dye) normalized to 250mm tumour volume). c, Ranking of the importance of the identified tumour-tissue biomarker features based on their assignment in the GTB decision trees (%, biomarker positive vessels of the number total vessels; no., number). The error bars indicate the standard deviaitoin (n=14).

When aiming to establish a biomarker for patient stratification, the practicality of the approach and the presence of a proper dynamic range are crucial. This implies that in the features identified via GTB, the functionality of tumour blood vessels needs to be excluded, because lectin cannot be injected in patients. For the fraction of VEGFR2+ blood vessels, the dynamic range is small (Supplementary Fig. 3l), making it unlikely to serve as a good biomarker. Moreover, as for the number of SMA+ and Col1+ blood vessels, double-staining would be required. This can be done preclinically with immunofluorescence, but is not typically performed in histopathological protocols in routine clinical practice. In follow-up studies with additional tumour models, we therefore focused on blood vessel and TAM density as tissue biomarkers.

The feature importance and biomarker potential of tumour blood vessels and TAM were confirmed in a panel of ten tumour models. This panel was selected to encompass models with very different tumour microenvironment architectures (thereby reflecting the heterogeneity observed in human tumours24) and consisted of six PDX and four CDX xenograft models. To ensure broad applicability of blood vessel and TAM density as biomarkers for predicting nanomedicine accumulation, we decided to employ a second drug-delivery system in these ten models, replacing the prototypic polymeric nanocarrier PHPMA with a PEGylated liposome formulation similar to Doxil/Caelyx25. Initially, fluorescent DiI-labelled liposomes were used to visualize the accumulation and distribution of liposomes in tumours. The highest levels of liposome accumulation were observed in E35CR and Calu-3 tumours, and the lowest levels were found in A549 and Calu-6 tumours (Fig. 4a).

a, Fluorescence microscopy analysis of Dil-labelled PEGylated liposomes (in red) in ten tumour models at 24h after i.v. administration Scale bar, 200m. The blood vessels are stained in green and the cell nuclei in blue. b, Tumour accumulation of PEGylated liposomal DXR in six PDX (green dots) and four CDX (red dots) tumour models. Individual and mean (black bars) tumour concentrations of DXR are shown for 20 mice per group and 5 mice per timepoint. c, Total tumour accumulation over time of PEGylated liposomal DXR (that is, AUC0120h). Values represent meanstandard error of the mean. d, Histopathological DAB staining of tumour blood vessels (CD31) and TAM (F4/80) for the ten models. Scale bars, 100m. eh, Quantification of blood vessel (e) and TAM (g) density based on DAB staining and correlation of blood vessel (f) and TAM (h) density with total liposomal DXR tumour accumulation (no., number of vessels or TAM per field of view).

We next used doxorubicin (DXR)-loaded liposomes and determined drug accumulation in tumours using high-performance liquid chromatography. For each of the ten models, this was done for four timepoints, with five tumours per timepoint (Fig. 4b). Total DXR concentrations over time were quantified and expressed as the area under the curve (AUC). In good agreement with the DiI-liposome fluorescence data (Fig. 4a), AUC determination demonstrated that tumour DXR concentrations were highest in E35CR and Calu-3, making these the highest drug-accumulating models, with drug levels three to five times higher than those of the majority of other models (Fig. 4c). A549 and Calu-6 were again found to accumulate the lowest amounts of liposomes, with DXR concentrations five to ten times lower than most other models. Interestingly, when comparing all AUC values together, it was furthermore found that PDX models presented with higher overall levels of liposomal DXR accumulation than CDX models (Fig. 4c).

In clinical practice, pathology protocols involve light (and not fluorescence) microscopy. Accordingly, we switched to 3,3-diaminobenzidine (DAB) staining and studied blood vessel and TAM density via standard histopathology in the ten PDX and CDX models. As shown in Fig. 4dh, we found that the three models with the lowest accumulation levels upon administration of liposomal DXR, that is, SW620, A549 and Calu-6 models (Fig. 4c), also presented with the lowest levels of CD31 and F4/80 staining. Across the ten different tumour models, there was a good correlation between tumour blood vessel and TAM density and nanomedicine accumulation (Fig. 4f,h). It should be noted in this regard, however, that the E35CR model was identified as a clear outlier, as it presented with the highest levels of Dil- and DXR-loaded liposome accumulation (Fig. 4ac), while its levels of CD31+ blood vessels were intermediate (Fig. 4f) and those of F4/80+ TAM were very low (Fig. 4g). When determining the area fraction of CD31 and F4/80 instead of the number of CD31+ and F4/80+ cells, observations were identical for all of the above notions, confirming the robustness of the tumour-tissue biomarkers identified (Supplementary Fig. 4). Altogether, these results demonstrate that there is a good correlation between the levels of the tumour blood vessels and TAM and the level of nanomedicine tumour accumulation.

Having identified tumour blood vessels and TAM as key features correlating with nanomedicine tumour accumulation, we next explored the robustness, validity and potential clinical applicability of combined tumour blood vessel and macrophage scoring, with the aim of developing a simple and straightforward biomarker protocol for patient stratification. This protocol is primarily designed to help predict which individuals from a heterogeneous patient population should be excluded in clinical trials, because their tumours are likely to show low nanomedicine accumulation and poor therapeutic efficacy (Fig. 5a).

a, Schematic workflow demonstrating the concept of patient stratification in cancer nanomedicine clinical translation based on tumour-tissue biopsies, created with BioRender.com. b, DAB staining illustrating the density of tumour blood vessels (CD31) and TAM (F4/80) in tumours, reaching from lowest (score 1) to highest (score 4) levels of blood vessel and macrophage density. Biomarker scores indicate 1 for absent, 2 for low, 3 for intermediate and 4 for high. Scale bars, 100m. c, Colour-coded heatmap, representing the distribution of CD31 and F4/80 product scores in the ten PDX and CDX tumour models with differing degrees of PEGylated liposomal DXR tumour accumulation. Tumours are ranked from high to low AUC, from top to bottom. Tumour-tissue biomarkers were scored by ten blinded observers, who each analysed three tissue sections per tumour model (n=30 in total). The colour intensity reflects the number of product scores. d, Schematic displaying the distribution of true and false positives and negatives in the tumour-tissue biomarker product score heatmap. e, Receiver operating characteristic (ROC) curve, generated on the basis of the tumour-tissue biomarker product scores, exemplifying very high diagnostic accuracy differentiating between low and high nanomedicine tumour accumulation (ROC curve is based on the scores in c; the red dashed line represents randomness and the units of the axis are in %).

We conceived a DAB-based histopathological scoring setup in which we considered 1 for absent, 2 for low, 3 for intermediate and 4 for high for the expression of both tumour-tissue biomarkers (Fig. 5b). Ten blinded observers, including three board-certified pathologists, were asked to score 60 tumour sections (30 for CD31 and 30 for F4/80; 6 for each tumour model). As shown in Fig. 5c, the colour-coded scoring intensities demonstrate that for tumour models with low CD31 and F4/80 product scores, the levels of liposomal DXR accumulation were also low. With a cut-off score of 6 to differentiate between tumours with low versus high nanomedicine accumulation, the blinded observers product scores correctly identified SW620, A549 and Calu-6 as true negatives (Figs. 4ac and 5c,d). Conversely, six out of seven models with good nanomedicine accumulation were correctly identified as true positives (Fig. 5c, d). The E35CR model turned out to be false negative, as its low CD31 and F4/80 product score incorrectly indicated that it would not accumulate liposomes well, which it clearly did do (Fig. 4ac). No false positives were detected (Fig. 5c,d). Altogether, nine out of ten tumour models could be correctly associated with low versus high nanomedicine accumulation on the basis of our tumour blood vessel and TAM biomarker product score.

To quantify the biomarker performance of our product score, we determined the area under the receiver operating characteristics (AUROC) curve. The AUROC curve represents a probability assessment, with a value of 0.5 resulting in a straight 45-line reflecting randomness (represented by the dashed red line in Fig. 5e). The AUROC curve represents the capability of a biomarker to distinguish between different classes, in this case between low versus high nanomedicine tumour accumulation. We obtained an AUROC value of 0.91 for our blood vessel and TAM product score (Fig. 5e), which is generally considered excellent for predicting nanomedicine tumour targeting, following the published criteria26.

The robustness and translatability of our biomarker product score were assessed in immunocompetent mouse models and in patient samples. The former were included to rule out the possibility that the presence of T cells plays an important role in determining nanomedicine delivery to tumours. To this end, we analysed PHPMA accumulation in orthotopic 4T1 triple-negative breast cancer tumours in BALB/c mice and PEGylated liposome accumulation in subcutaneous and orthotopic Hep55.1C liver tumours in C57BL/6J mice. As shown in Supplementary Fig. 5, good correlations between blood vessel and TAM product scores and nanomedicine tumour targeting were observed, as exemplified by R2 values of 0.51, 0.86 and 0.63, respectively. This confirms that our biomarker product score remains valid in syngeneic and orthotopic tumours in immunocompetent mice.

Next, we aligned our biomarker product score with the most comprehensive clinical dataset available on nanomedicine tumour targeting in patients27. In this study, the researchers used 111In-labelled PEGylated liposomes and quantitative SPECT imaging to assess nanomedicine tumour accumulation in 17 patients with different type of tumour27. For the most prevalent tumour types included, that is, ductal breast cancer, squamous cell carcinoma of the lung and squamous cell head and neck cancer, we collected matching tumour resection samples as well as primary tumour biopsies from the Biobank archive of the Institute of Pathology at RWTH Aachen University Hospital (Supplementary Table 5). Blood vessel (CD31+) and TAM (CD68+) density were analysed in ten different patient samples for each of the three cancer types, always in five different microarray sections for each individual tumour specimen. The expression levels and patterns of F4/80 and CD68 on TAM were demonstrated to be similar (Supplementary Fig. 6). Representative CD31 and CD68 stainings for breast, lung and head and neck cancer lesions are shown in Fig. 6a,b. Using QuPath software28, we quantified blood vessel and TAM density in these tumours and found that breast cancer typically presents with much lower levels of both tumour-tissue biomarkers as compared with lung and head and neck cancer (P<0.001 and P<0.0001 for blood vessels and P<0.05 for TAM; Fig. 6c,d).

a,b, Representative DAB stainings of blood vessels (a) and TAM (b) in tumour tissues obtained from patients with breast, lung and head and neck (H&N) cancer (all data in this figurre are based on tumour resections, and the data based on biopsies are shown in Supplementary Fig. 7). c,d, Quantification of blood vessels (c) and TAM (d) in ten patient samples for each tumour type (no., number per field of view; significance is indicated in P values based on Students t-test). e, Tumour accumulation of 111In-labelled PEGylated liposomes in patients with breast, lung and head and neck (H&N) cancer (in percentage of the injected dose per kilogram tumour). The data are replotted based on the work in ref. 27 (significance is indicated in P values based on Students t-test). f, Means of blood vessel and TAM product scores plotted against means of liposome tumour targeting, showing that biomarker product scoring correctly identifies breast cancers as poorly nanomedicine accumulating lesions. The error bars indicate the distribution of %ID and product score values (standard deviations on the x-axis and minima and maxima on the y-axis; n=310 as it is based on the means of c, d and e).

The liposome tumour targeting data from ref. 27 is replotted in Fig. 6e. In line with our rationale and reasoning, it can be seen that ductal breast cancer lesions in patients (5.33.0%IDkg1) accumulate radiolabelled PEGylated liposomes significantly less well than lung (18.26.6%IDkg1; P<0.05) and head and neck (33.017.6%IDkg1; P<0.05) squamous cell carcinomas. When generating tumour-tissue biomarker product scores based on the number of blood vessels and TAM per tumour type and when plotting these product scores against the average level of liposome accumulation per tumour type, we found that breast cancers clustered in the lower left corner, thereby pinpointing them as true negatives (Fig. 6f). For the majority of lung and head and neck cancer lesions, the product scores were much higher than for breast cancer, thereby classifying them as true positives. In a final validation study, we also employed the original primary tumour biopsies for biomarker assessment. For the 30 patients samples initially included, 28 primary biopsies were available. As exemplified by Figure S7, the results obtained in biopsies are very similar to those obtained in resected tumour tissues, again clearly identifying ductal breast cancers as poorly accumulating lesions. Thereby, they not only confirm the robustness of our approach but also showcase its clinical translatability. Altogether, these findings provide compelling proof-of-concept for the use of tumour blood vessels and TAM as tissue biomarkers for predicting nanomedicine tumour targeting.

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Histopathological biomarkers for predicting the tumour accumulation of nanomedicines - Nature.com

Oxford and Cardiff alumni named BSNM Champion in Nanomedicine – News from Wales

Dr. Aadarsh Mishra, 27, an alumnus of Oxford University and Cardiff University has been named as the Champion of The British Society for Nanomedicine. Aadarsh graduated with a First Class Honours in Mechanical Engineering from Cardiff University in 2017.

The British Society for Nanomedicine is the primary UK nanomedicine society which aims to raise awareness of nanomedicine research while fostering collaboration with industry, academia, clinicians and the public. The Champions of the British Society for Nanomedicine act as a local ambassador for the society, and include early career researchers, lecturers, and professors.

Aadarshs research involves rheology and biomechanical modelling of agarose gels and soft tissues. In the past, agar has been used as a multifunctional encapsulating material and as a drug carrier. Aadarsh has been particularly working with agarose hydrogels and investigating their biomechanical properties as a soft tissue mimic. His work will lead to a better understanding of the agarose-tissue response in time and frequency domain. During his research, Aadarsh has mimicked heart and kidney tissues using agarose hydrogels which will have potential applications in elastography techniques such as Magnetic Resonance Elastography (MRE), Acoustic Radiation Force Impulse Imaging (ARFI) and Shear Wave Elastography (SWE). Moreover, the agarose mimicking kidney will have potential applications during lithotripsy technique (for kidney stone treatment).

Aadarsh worked with Alesi Surgical Ltd. (Cardiff) as a Research and Development (R&D) Engineer (from 2015-17) and co-invented the design electrode shield which was later filed as an international patent. At the age of 21, Aadarsh co-authored a high-impact factor paper in Nano Letters (published by American Chemical Society) where he performed Finite Element Analysis (FEA) simulations. Aadarsh has also worked at the Indian Institute of Technology (IIT Delhi) on a defence project where he was developing experimental setups for high strain rate testing. In 2014, Aadarsh pursued his research internship at the Indian Institute of Science (IISc, Bangalore) on a project related to Tribology.

Aadarsh has also published a chapter in the book Power Ultrasonics and presented his work at several international conferences such as Annual European Rheology Conference and 18th European Mechanics of Materials Conference. Aadarsh was also elected as the Fellow of Royal Astronomical Society at 19 years of age.

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Oxford and Cardiff alumni named BSNM Champion in Nanomedicine - News from Wales

Understanding the Protein Corona in Nanomedicine – Medriva

Understanding the Protein Corona in Nanomedicine

As nanomedicine continues to expand its horizons in the field of therapeutic nucleic acid delivery and beyond, understanding the protein corona, a layer of biomolecules that forms on nanoparticles in biological fluids, is of critical importance. This protein layer plays a pivotal role in determining the safety and efficacy of nanomedicine.

A recent multi-center study involving 17 proteomics facilities underscored the significance of this layer, revealing substantial data variability. Remarkably, only 1.8% of proteins were consistently identified across these centers, indicating the need for a harmonized approach to nanoparticle protein corona analysis.

The study further illuminated the importance of standardizing procedures in protein corona analysis. The implementation of an aggregated database search with uniform parameters proved instrumental in harmonizing proteomics data, increasing the reproducibility and the percentage of consistently identified unique proteins across distinct cores.

More specifically, the study found that reduction and alkylation are crucial steps in protein corona sample processing, with the omission of these steps reducing the number of total quantified peptides by around 20%. Thus, uniform data processing pipelines can play a major role in enhancing the reproducibility of protein corona analysis.

Just like plasma proteomics, protein corona analysis faces an array of challenges, including a broad dynamic range and the presence of different protein isoforms. Furthermore, the composition of the protein corona determines how biosystems perceive nanoparticles, a factor that can lead to biased data interpretation if low-abundant genuine targets are not detected. The quality and proteome coverage of protein corona reported by core facilities can be affected by various factors, further underscoring the need for standardization across different proteomics studies.

The study also investigated the influence of database search, data extraction, processing, and analysis on observed data heterogeneity, laying the groundwork for future research to standardize and harmonize results. This is particularly important in the realm of nanomedicine, where protein-based nanoparticles show immense potential for therapeutic nucleic acid delivery, owing to their unique properties such as biodegradability, biocompatibility, and ease of functionalization.

Looking forward, the standardization and harmonization of protein corona data will be instrumental in overcoming barriers to effective protein nanoparticle-mediated nucleic acid delivery. It will also aid in the development of non-viral protein materials for nucleic acid delivery, and in the design of smart drug delivery systems (DDS) that specifically target pathologic tissues while minimizing off-target effects on healthy tissues.

By addressing these challenges and advancing clinical applications of nanoscale biotechnologies, we may be one step closer to realizing the full potential of nanomedicine, from insulin injections and treatment of rheumatoid arthritis to monitoring oxygen levels and overcoming barriers to nanoparticle penetration into tumors.

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Understanding the Protein Corona in Nanomedicine - Medriva

Immunoregulatory nanomedicine for respiratory infections – Nature.com

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Immunoregulatory nanomedicine for respiratory infections - Nature.com

Nano-Particles Show Promise in Treating Infectious Diseases – Mirage News

The COVID-19 pandemic demonstrated the importance of being prepared with drug interventions to contain viral outbreaks that can otherwise have devastating consequences. In preparing for the next pandemicor Disease X, there is an urgent need for versatile platform technologies that could be repurposed upon short notice, to combat infectious outbreaks.

A team of researchers, led by Assistant Professor Minh Le from the Institute for Digital Medicine (WisDM) and Department of Pharmacology at the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine), discovered that nano-sized particles released by cells, termed "extracellular vesicles" (EVs), can curb the viral infectivity of SARS-CoV-2its wild type and variant strainsand potentially other infectious diseases. Asst Prof Le said, "Our study showed that these cell-derived nanoparticles are effective carriers of drugs that target viral genes precisely. These EVs are therefore an efficient tool for therapeutic intervention in patients who are infected with COVID-19 or other infectious diseases."

The study, conducted in collaboration with NUS Medicine's Biosafety Level 3 (BSL3) Core Facility, the Cancer Science Institute of Singapore at National University of Singapore, and the School of Physical and Mathematical Sciences at Nanyang Technological University (NTU), demonstrated potent inhibition of COVID-19 infection in laboratory models using a combination of EV-based inhibition and anti-sense RNA therapy mediated by antisense oligonucleotides (ASOs). A versatile tool that can be applied to any gene of interest, ASOs can recognise and bind to complementary regions of target RNA molecules and induce their inhibition and degradation.

In the study, published in ACS Nano, the authors utilised human red blood cell-derived EVs to deliver ASOs to key sites infected with SARS-CoV-2, resulting in efficient suppression of SARS-CoV-2 infection and replication. The researchers also discovered that EVs exhibited distinct antiviral properties, capable of inhibiting phosphatidylserine (PS) receptor-mediated pathways of viral infectiona key pathway utilised by many viruses to facilitate viral infection. These viral inhibitory mechanisms were applicable to multiple variants of SARS-CoV-2, including the Delta and Omicron strains, ensuring their broad effectiveness against SARS-CoV-2 infection.

The results from the study point to anti-sense RNA therapy with ASOs as a potentially effective approach that could serve to combat future viral outbreaks. The platform that was developed to deliver ASOs through EVs to target the SARS-CoV-2 viral genes can be readily applied to treat other viral infections by replacing the ASO sequences with those complementary to the target viral genes. Asst Prof Le and her graduate students Migara Jay and Gao Chang, the first authors of the study, are currently developing more potent combinations of ASOs with the help of artificial intelligence prediction models to achieve enhanced viral inhibition. This collaborative effort includes partnership with the research teams of Associate Professor Edward Chow from WisDM, NUS Medicine, and NUS Medicine's BSL3 Core Facility.

Associate Professor Justin Chu, Director of the BSL3 Core Facility at NUS Medicine, and co-author of the study, added, "This remarkable extracellular vesicle-based delivery platform technology coupled with anti-viral therapy is highly promising to combat a broad range of viruses and even Disease X." The latter is a general description for emerging and unknown infectious threats, such as novel coronaviruses. The term was used to alert and encourage the development of platform technologies, including vaccines, drug therapies and diagnostic tests, which could be quickly customised and then deployed against future epidemic and pandemic outbreaks. Assoc Prof Chu is also from the Infectious Diseases Translational Research Programme at NUS Medicine.

Professor Dean Ho, Provost's Chair Professor and Director of WisDM at NUS Medicine, said, "This work brings the scalable and well-tolerated extracellular vesicle-based drug delivery platform an important step closer towards clinical validation studies."

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Nano-Particles Show Promise in Treating Infectious Diseases - Mirage News

Building Trust and Fostering Collaborations Key to Startup Formation – Weill Cornell Medicine Newsroom

One of the hardest points on the translational road from bench to bedside can be the point where you have to turn over your discovery to a company youve foundeda company whose subsequent direction you wont fully control.

Its sort of your baby that youre turning over, said Dr. Ronald Crystal, chair of the Department of Genetic Medicine and the Bruce Webster Professor of Internal Medicine at Weill Cornell Medicine, gene therapy pioneer and four-time startup founder. But youve got to be willing to let go of it; it takes a village to develop a new drug.

Dr. Crystal and others recounted recent entrepreneurial journeysin his case, to bring a gene therapy for refractory angina to the clinicat the seventh annual Deans Symposium onInnovation and Entrepreneurship, hosted by Enterprise Innovation on Nov. 7 in the Griffis Faculty Club. Now an established tradition, the Deans Symposium celebrates innovation and Weill Cornell Medicines entrepreneurial spirit, and showcases the institutions support for faculty and trainees who want to bring their discoveries to market to benefit a large patient population.

Dr. Robert Harrington speaks during the Dean's Symposium on Innovation and Entrepreneurship.

You are part of a medical college that has a history of innovation, Dr. Robert Harrington, the Stephen and Suzanne Weiss Dean of Weill Cornell Medicine reminded attendees, citing the example of Weill Cornells Dr. Georgios Papanikolaou, developer of the Pap Smear a century ago. Dr. Harrington noted that, thanks to Weill Cornell Medicines network of programs supporting translational research, there are currently 44 active startups founded by institutional researchers, with a total of nearly $2 billion in funding, including from top-tier venture capital firms.

Dr. Krystyn Van Vliet, Cornell Universitys vice president for research and innovation, emphasized that the journey from discovery to commercialization requires much resilience and expertise, which is why a team that helps guide the harder steps of our investors is so important.

Dr. John Leonard, senior associate dean for innovation and initiatives, discussed the recent expansion of Weill Cornell Medicine Enterprise Innovations team of experts and entrepreneurial programs.

It's really important to keep in mind that our remit here, and the opportunities, are broad, Dr. Leonard said, noting that Enterprise Innovation partners with innovators to develop not only therapeutics and medical devices but also diagnostics, laboratory tools and software tools for clinical and research applications.

Dr. John Leonard

If youre working in these areas, there are opportunities to take your findings forward in different ways, said Dr. Leonard, who is also interim chair of the Weill Department of Medicine and the Richard T. Silver Distinguished Professor of Hematology and Medical Oncology at Weill Cornell Medicine.

Keynote speaker Dr. Sangeeta Bhatia, a physician, biomedical engineer and serial inventor/entrepreneur who is the John J. and Dorothy Wilson Professor of Engineering and director of the Laboratory for Multiscale Regenerative Technologies at M.I.T., offered an appealing picture of translational success as she discussed some of her many inventions. These include a human-liver-on-a-chip device that pharma companies can use to study drug metabolism without posing risks to patients; an injectable set of nano-sensors that can be collected in urine to provide a multiplex readout of liver health as an alternative to liver biopsy; and a liver-cell-based therapy for treating liver disease.

Dr. Bhatia highlighted that now is a great time for biomedical and biotech entrepreneurs, given the advances and convergences in miniaturization, artificial intelligence, stem cell methods, genomics and other relevant, cutting-edge technologies.

She noted too that female academics, though underrepresented in startups, are getting more support and resources than ever. At M.I.T., for example, Dr. Bhatia recently helped start the Faculty Founder Initiative, which provides skilled mentorship, funding, legal advice, lab space and other resources to female faculty. She stressed that there are ways to minimize conflicts between entrepreneurship and family life, recounting how her first startup was hatched with colleagues in the hours after her youngest daughter went to bed, whereas for a subsequent venture, during the pandemic, she and her co-founders raised most of the initial funding via Zoom.

For those of you who have young families, it doesnt have to be that youre always going to dinners and getting on planesthere are all kinds of ways to do it, she said.

Dr. Bhatia also underscored that entrepreneurship tends to be easier when one doesnt go it alone.

It can be lonely and stressfulyoure doing something no ones ever done before and there are no right answers, and that can keep you up at night, she said. Its so much more fun to be on that ride with a colleague that you like and trust.

Trust, and willingness to bring others into ones circle of trust, was a theme echoed by Dr. Crystal and his colleague Albert Gianchetti, CEO of Xylocor Therapeutics, the startup now developing the angina gene therapy. In a discussion moderated by Dr. Lisa Placanica, senior managing director of Center for Technology Licensing at Weill Cornell Medicine, the scientist and seasoned pharma CEO spoke about hurdles overcome and lessons learned.

The biotech side, the business side, is like a whole different world, and you learn that the people involved on that side are really smart about that side of thingsthey may not know the things we scientists know, but we dont know the things they know, Dr. Crystal said.

The stories highlighted the key events in the science-to-startup journey: the initial high-impact scientific publication; the recognition of translational potential; the filing of patent applications and the drafting of a business plan; the acquisition of a mentor or mentors; the search for seed money and a founding CEO; the months-to-years-long hunt for that first big (Series A) investment, from venture capital investors or an established pharma company; and lastlyparticularly for therapeutic venturesthe first tests in patients.

You get better at it over time, Dr. Bhatia said. You develop a keener sense of what a company needs to make it to the next level, and at the same time your network of connections with investors and entrepreneurs is expanding.

Even so, she added, each entrepreneurial journey is different, and involves its own challenges and pitfalls.

Dr. Crystal reiterated this point during his fireside chat. I would advise the budding entrepreneurs in the audience to use the resources we have here to help you avoid some of those pitfalls, he said.

Naturally, all spoke of the satisfactionat the end of that entrepreneurial roadof being able to improve patients lives.

One of the most exciting things for me, Gianchetti said, was when we went out and interviewed patients who did very well in a trial, and they were talking about how much better they feltone asked, When can my family make an investment in this company? Because what you guys did for me was a miracle.

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Building Trust and Fostering Collaborations Key to Startup Formation - Weill Cornell Medicine Newsroom

UNSW picks up lion’s share of Royal Society of NSW Awards – UNSW Newsroom

Six UNSW researchers and professional staff have been recognised at the 2023 Royal Society of NSW Awards. Scientia Professor Helen Christensen has been awarded the James Cook Medal, which is the Societys highest honour. Professor Maria Kavallaris, Scientia Professor Kaarin Anstey, Dr Brendon Neuen, Professor Moninya Roughan and Mr Jason Antony have also received awards.

Overall, eight awards and medals, three scholarships and two service awards were announced for 2023 by the Royal Society of NSW at the 1318th Ordinary General Meeting, held at the State Library in NSW Wednesday night. The Open Lecture was delivered by UNSW Professor John Church, winner of the Societys 2022 James Cook Medal.

Interim Dean of UNSW Medicine & Health Professor Adrienne Torda applauded the UNSW winners on their success.

"I congratulate these extraordinary UNSW researchers for being recognised at the Royal Society of New South Wales Awards.Special congratulations to Helen Christensen for receiving the James Cook Medal. Helen is a truly deserving recipient as one of Australias leading mental health experts, she has made significant contributions to being able to identify and treat sufferers of this chronic disease through innovative digital treatments, Prof. Torda said.

All our winners are exceptional specialists in their fields. The annual Royal Society of NSW awards are among the oldest and most prestigious awards in Australia, and its an honour for so many of our scientists to be recognised.

UNSW Scientia Professor Helen Christensen, Board Director of the Black Dog Institute, has been awarded the James Cook Medal for outstanding contributions to science and human welfare in the Southern Hemisphere. Its the most prestigious award offered by the Royal Society of NSW.

Prof. Christensen is a leading expert on using technology to deliver evidence-based interventions for the prevention and treatment of depression, anxiety, suicide, and self-harm.

I'm very honoured to receive this prestigious medal. The work I do, alongside my colleagues, is all about making life better for those in our community facing mental health struggles. The Royal Societys award recognises that using science is one of the best ways to solve the tough problems we're dealing with today, Prof. Christensen said.

Read more: UNSW researchers awarded $10m in health funding

UNSW researchers have received the James Cook Medal nine of the last 10 times the medal has been awarded.

Professor Moninya Roughan. Photo: UNSW.

Professor Moninya Roughan from UNSW Science has been awarded the Clarke Medal for distinguished research in the natural sciences, conducted in Australia and its territories, in the fields of botany, zoology, and geology.

Prof. Roughan is an authority on the dynamics of the East Australian Current, ocean observationand prediction systems and their application to understanding western boundary currents and continental shelf processes. She leads the Coastal and Regional Oceanography Lab at UNSW.

I am truly humbled and deeply grateful to be the recipient of this prestigious award. This recognition is not just a reflection of my individual efforts but a testament to the collaborative spirit of the scientific community and every breakthrough stands on the shoulders of those who came before me. I am fortunate to have been guided by mentors, inspired by colleagues, and supported by my dedicated research team at UNSW, Prof. Roughan said.

"I believe that the truest achievement is in the positive impact my research has on the world and I hope that this recognition inspires future generations to explore the limitless possibilities in the ocean sciences and foster environmental stewardship."

Professor Maria Kavallaris. Photo: UNSW.

Professor Maria Kavallaris from UNSW Medicine & Health received the Walter Burfitt Award, for distinguished research in any area of the Medical and Veterinary Sciences and Technologies.

Prof. Kavallaris leads the Tumour Biology and Targeting Group at the Childrens Cancer Institute and is the founding co-director of the Australian Centre for NanoMedicine at UNSW. She has made seminal contributions to understanding the role of the cytoskeleton in cancer biology andis best known for identifying how tumour cells become resistant to commonly used chemotherapydrugs and how drug resistance can be reversed.

Read more:New treatment approach to selectively target cancer cells: study

Her studies have identified how some tumours can grow and spread in the body, and she has applied this knowledge towards the development of advanced diagnostics and therapeutics using nanotechnology.

I've dedicated my life to understanding and identifying effective treatments for cancer because I believe that everyone deserves a chance to survive. This award is a reminder that our work is making a difference, and it inspires me to continue pushing forward. This award is not just for me; it's for all the past and present brilliant students and researchers who I have had the honour of mentoring and working with, Prof. Kavallaris said.

Scientia Professor Kaarin Anstey. Photo: UNSW.

Scientia Professor Kaarin Anstey from UNSW Science has received the inaugural Award in the Social and Behavioural Sciences, which is for distinguished research in any area of the social and behavioural sciences including psychology, economics, management, and related disciplines.

Read more:Chef's kiss: brain-friendly cake shines light on cognitive decline

Prof. Ansteys research programs focus on cognitive resilience in ageing as well as prevention of dementia. She has developed new methods to assess risk of cognitive decline and dementia as well as non-pharmacological interventions to reduce these risks. Another focus of her work is on older driver safety and in this field, she has also developed and validated risk assessment tools and interventions.

I am excited and honoured to receive this inaugural award from the Royal Society of NSW and would like to thank my colleagues and team with whom Ive worked for many years, Prof. Anstey said.

Cognitive health is central to ageing well and I look forward to continuing to expand our knowledge in this field.

Dr Brendon Neuen from the George Institute of Global Health an affiliate of UNSW has been awarded the inaugural Ida Browne Early Career Medal. The Medal is awarded for contributions to knowledge and society in Australia or its territories by an individual from 05 years post-PhD or equivalent.

Dr Neuen is a nephrologist and Director of the Kidney Trials Unit at Royal North Shore Hospital. He is recognised for his expertise in cardio-renal-metabolic medicine. His work has directly informed more than 25 major international and national guidelines, position papers and scientific statements about optimal care for people with type 2 diabetes and kidney disease.

I am delighted and honoured to be the inaugural recipient of the Ida Browne Medal from the Royal Society of NSW. My work would not be possible without the generosity of patients and thededicationofstudy teams and investigatorswho made large-scale internationalclinical trialsa reality, Dr Neuen said.

I feel a deep sense of responsibility to ensure that this recognitionis translated intoa long and impactful career in clinical trialsthat improves the lives of people with type 2 diabetes and kidney disease worldwide."

Jason Antony. Photo: UNSW

Mr Jason Antony from the Industrial Relations Research Group atUNSW Canberra has received the Royal Society of New South Wales Citation, for significant contributions to the Society.

Since 2016, Mr Antony has been indispensable in the production of fifteen issues of the Journal & Proceedings of the Royal Society, and as editor and producer, of 28 issues of the Bulletin from 2020 to 2023.

Helping produce the Royal Societys Journal & Proceedings and Bulletinis a rewarding and enriching experience, Mr Antony said.

When a venerable institution recognises one'scontributions formally, it fills life with vim, vigour, and a renewed sense of purpose. I am immensely grateful to the Society, and to the myriad ofwise, wonderful people who have provided guidance and nurtured my skills over the years.

Read more about the Royal Society of NSW Awards 2023.

Link:
UNSW picks up lion's share of Royal Society of NSW Awards - UNSW Newsroom

NOT-AR-23-022: Request for Information on Themes for the NIAMS … – National Institutes of Health (.gov)

Request for Information on Themes for the NIAMS Strategic Plan for Fiscal Years 2025-2029

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) supports research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. NIAMS is updating its Strategic Plan to help guide the research, training, and information dissemination programs it supports between fiscal years 2025 through 2029. The new Plan will focus on cross-cutting thematic research opportunities that position the Institute to make a difference in the lives of all Americans.Because public input is a crucial step in this effort, the Institute issued a Request for Information (NOT-AR-22-023) and hosted a meeting attended by approximately 160 researchers, patient representatives, and staff from other Federal entities to gain insight into topics that could be included in the new Strategic Plan.

Through this Request for Information, NIAMS invites feedback from researchers in academia and industry, health care professionals, patient advocates and health advocacy organizations, scientific or professional organizations, Federal agencies, and other interested members of the public on the Institutes distillation of the input received to date. Professional societies and patient organizations are strongly encouraged to submit a single response that reflects the views of their entire membership.

Please provide your perspective on the following potential cross-cutting themes, examples, and bold aspirations. NIAMS is particularly interested in suggestions for additional or alternative:

Examples:

Bold Aspirations:

Examples:

Bold Aspiration:

Note: Efforts to identify and reduce health disparities and provide all Americans with equitable access to clinical and epidemiologic studies and healthcare should be considered for NIAMS-funded research projects whenever possible.

Examples:

Bold Aspirations:

Examples:

Bold Aspiration:

Note: Consistent with the note under Health disparities and health equity, studies of lifestyle factors and environmental exposures should include efforts to identify and reduce health disparities and provide all Americans with equitable access to clinical and epidemiologic studies and healthcare whenever possible.

Examples:

Bold Aspiration:

Note: Consistent with the note under Health disparities and health equity, clinical and epidemiologic research should include efforts to identify and reduce health disparities and provide all Americans with equitable access to clinical and epidemiologic studies and healthcare whenever possible.

Examples:

Bold Aspiration:

Examples:

Bold Aspiration:

Note: Training and workforce efforts are essential for the pursuit of all cross-cutting thematic research areas in the new NIAMS Strategic Plan.

Examples:

Bold Aspiration:

Examples:

Bold Aspirations:

Responses to this RFI must be submitted electronically at https://rfi.grants.nih.gov/?s=654a7bc81e7ccb6f7d03d792.

Responses must be received by Monday, January 1, 2024.

Responses to this RFI are voluntary. Do not include any proprietary, classified, confidential, trade secret, or sensitive information in your response. The responses will be reviewed by NIAMS staff, leadership, and Advisory Council members. Individual feedback will not be provided to any respondent. NIAMS will use the information submitted in response to this RFI at its discretion and will not provide comments to any respondents submission. Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted.The Government reserves the right to use any submitted information on public NIH websites, in reports, in summaries of the state of the science, in any possible resultant solicitation(s), grant(s), or cooperative agreement(s), or in the development of future funding opportunity announcements.

This RFI is for information and planning purposes only and shall not be construed as a solicitation, grant, or cooperative agreement, or as an obligation on the part of the Federal Government, the NIH, or individual NIH Institutes and Centers to provide support for any ideas identified in response to it. The Government will not pay for the preparation of any information submitted or for the Governments use of such information. No basis for claims against the U.S. Government shall arise as a result of a response to this request for information or from the Governments use of such information.

We look forward to your input and hope that you will share this RFI document with your colleagues.

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NOT-AR-23-022: Request for Information on Themes for the NIAMS ... - National Institutes of Health (.gov)

The effects of exposure to O2- and HOCl-nanobubble water on … – Nature.com

Clinical parameters of the participants

Table 1 shows clinical parameter of the participants. The median age was 53.5years (Interquartile range (IQR) 45.868.0), and the median number of teeth was 25.5 (IQR 23.028.0). Of the total number of 153 periodontal sites, the median number of pockets less than 3mm was 123.50 (IQR 101.80147.00), the median number of pockets 4mm was 16 (IQR 3.7528.25), and the median number of pockets greater than 5mm was 1.5 (IQR 0.008.00).

In this study, salivary microbiota composition of 16 patients was studied based on the sequencing of the 16S rRNA gene. The samples provided 2,092,625 quality reads corresponding to the V3V4 regions of the 16S rRNA gene sequences, which were subsequently assigned to 308 species-level operational taxonomic units (OTUs) based on~97% sequence similarity. We investigated the changes of alpha-diversity due to exposure to NBW. In observed features, O2-NBW and HOCl-NBW tended to decrease alpha-diversity relative to the control; however, the differences were not significant (P=0.85). Shannon index also did not show significant differences (P=0.79) (Supplementary Fig.1). Figure1 shows the scatter diagram of beta-diversity based on Principal Coordinate Analysis (PCoA). In the Unweighted UniFraq distance, there was no significant difference between control and O2-NBW (P=0.168) or between control and HOCl-NBW (P=0.916) (Fig.1A). Similarly, there was no significant difference between control and O2-NBW or HOCl-NBW at the Weighted UniFrac distance (Fig.1B, P=0.521; P=0.828, respectively).

Beta-diversity of unweighted UniFraq distance (A) and weighted UniFraq distance (B). Colored dots indicate individual sample groups: Black: Control; red: O2-NBW; green: HOCl-NBW. Colored circles indicate groups exposed to NBW; Black: Control; Red: O2-NBW; Green: HOCl-NBW.

Supplementary Fig.2 shows the relative frequencies of the different salivary bacteria. The bacterial genera, based on detection in 1% or more of the total population of the salivary microbiome, were composed of 71 OTUs (frequency>0.001) (Supplementary Fig.2A). Specifically, 14 major genera including Prevotella, Streptococcus, Veillonella, Neisseria, Haemophilus, Leptotrichia, Porphyromonas, Fusobacterium, Rothia, Graulicatella, Alloprevotella, Campylobacter, Atopobium, Saccharibacteria (TM7) [G-1] were detected. In similar analyses, bacterial species that were detected in 1% and more of the salivary microbiome, constituted 166 OTUs (frequence>0.001) and included 25 major species, namely Prevotella melaninogenica, Haemophilus parainfluenzae, Streptococcus salivarius, Neisseria spp., Porphyromonas pasteri, Veillonella dispar, Streptococcus spp., Rothia mucilaginosa, Fusobacterium periodonticum, Veillonella atypica, Leptotrichia sp. HMT417, Prevotella pallens, Veillonella parvula, Veillonella rogosae, Prevotella spp., Granulicatella adiacens, Leptotrichia sp. HMT221, Streptococcus parasanguinis clade411, Neisseria subflava, Prevotella sp. HMT313, Prevotella salivae, Campylobacter concisus, Leptotrichia sp. HMT215, Saccharibacteria (TM7) [G-1] bacterium HMT352, Atopobium parvulum.

We next investigated the relative abundance in the control and exposed groups by bacterial genera. Repeat measures ANOVA for the 14 bacterial genera with detection rates greater than 1% showed that only the genus Porphyromonas had a significant association among the three groups. Multiple testing also revealed significant associations between control and O2-NBW (P=0.044) and between control and HOCl-NBW (P=0.007) in the genus Porphyromonas (Table 2). Also, we investigated the relative abundance in the control and exposed groups by bacterial species. Repeated measures analysis of variance for the 25 bacterial species with detection rates greater than 1% showed that only P. pasteri was significantly associated among the three groups (P=0.008). Multiple testing also showed a significant reduction (1.066%) in P. pasteri (P=0.028) between control and HOCl-NBW (Table 3).

Figure2 shows the results of the hierarchical cluster analysis by Wards method based on the results of the PCoA, which revealed two subclusters in terms of both Unweighted UniFraq distance (Fig.2A) and Weighted UniFraq distance (Fig.2B). In Fig.2A, CL1 and CL2 were formed, with CL1 having 10 subjects and CL2 having 6 subjects. In Fig.2B, CL3 and CL4 were formed, with CL3 comprising 9 subjects and CL4 7 subjects.

Results of cluster analysis of relative abundance in oral microbiome (N=16). (A) Unweighted cluster. (B) Weighted cluster. Stratified cluster analyses were performed according to the Ward method based on the results of PCoA. Numbers indicate sample ID. Clustering was performed using the Ward method with Euclidian Distance.

Supplementary Fig.3 shows the results of the principal coordinates analysis of the Unweighted UniFraq distance (A, B), and the Weighted UniFrac distance (C, D). Supplementary Fig.3A shows the results between Control and O2-NBW, and Supplementary Fig.3B shows the results between Control and HOCl-NBW. In Supplementary Fig.3A, there was no significant difference between the two groups in CL1 (P=0.536), while in CL2 there was a significant difference between the two groups (P=0.033). On the other hand, in Supplementary Fig.3B, there was no significant difference between CL1 and CL2.

In contrast, Supplementary Fig.3C,D show the results of the principal coordinates analysis of the Weighted UniFraq distance. Supplementary Fig.3C shows the results for control and O2-NBW, and Supplementary Fig.3D shows the results for control and HOCl-NBW. There were no significant differences between the two groups for both CL3 and CL4 in Supplementary Fig.3C,D.

We investigated the relative abundance of bacterial genera in CL1 and CL2 in the Unweighted cluster; no bacterial genera were significantly different in both CL1 and CL2. Also, in bacterial species, no bacterial species were found to have a significant difference between CL1 and CL2 (Supplementary Table 1).

On the other hand, in the relative abundance of bacterial genera in CL3 in the weighted clusters, the only significant reduction (1.186%) between Control and HOCl-NBW was observed in the genus Porphyromonas (Table 4). However, no bacterial genus showed significant differences in CL4. In the relative abundance of bacterial species, only P. pasteri showed significant reduction (0.921%) among the bacterial species in the CL3. On the other hand, no significant differences were found among the bacterial species in the CL4 (Table 5).

Tables 6 and 7 show the clinical parameters of the subjects according to cluster. Table 6 shows the Unweighted results; the categories that showed significant differences between CL1 and CL2 were the number of probing pocket depth (PD)s less than 3mm, the number of PDs 4mm, and the number of PDs greater than 5mm. No significant differences were found in the other categories. Table 7 shows the weighted results, where the category that showed a significant difference between CL3 and CL4 was the number of PDs of 4mm. No significant differences were found in the other categories.

Figure3 shows a scatter plot between PD values and difference in relative abundance in CL3 (N=9), the cluster where a significant association between Control and HOCl-NBW was observed in Tables 4 and 5. As shown in Fig.3B, t=2.45 at PD=4mm, indicating that the higher the number of PD=4mm, the higher the effect of HOCl-NBW exposure on P. pasteri. On the other hand, no significant association was found for PD=3mm or less and PD=5mm or more. These results suggest that relative abundance of P. pasteri is associated with clinical signs of early stage of periodontitis.

Scatter plots and correlation coefficient tests in CL3 group (N=9). Spearmans rank correlation coefficient. Alternative hypothesis: true is greater than 0. The significance level was set at alpha=0.05. (A) Spearmans rank correlation coefficient0.0667 (P=0.58). (B) Spearmans rank correlation coefficient 0.653 (P=0.028). (C) Spearmans rank correlation coefficient 0.131(P=0.37).

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The effects of exposure to O2- and HOCl-nanobubble water on ... - Nature.com

Brain Study Suggests Traumatic Memories Are Processed as … – Slashdot

Traumatic memories had their own neural mechanism, brain scans showed, which may help explain their vivid and intrusive nature. From a report: At the root of post-traumatic stress disorder, or PTSD, is a memory that cannot be controlled. It may intrude on everyday activity, thrusting a person into the middle of a horrifying event, or surface as night terrors or flashbacks. Decades of treatment of military veterans and sexual assault survivors have left little doubt that traumatic memories function differently from other memories. A group of researchers at Yale University and the Icahn School of Medicine at Mount Sinai set out to find empirical evidence of those differences.

The team conducted brain scans of 28 people with PTSD while they listened to recorded narrations of their own memories. Some of the recorded memories were neutral, some were simply "sad," and some were traumatic. The brain scans found clear differences, the researchers reported in a paper published on Thursday in the journal Nature Neuroscience. The people listening to the sad memories, which often involved the death of a family member, showed consistently high engagement of the hippocampus, part of the brain that organizes and contextualizes memories. When the same people listened to their traumatic memories -- of sexual assaults, fires, school shootings and terrorist attacks -- the hippocampus was not involved.

[...] Indeed, the authors conclude in the paper, "traumatic memories are not experienced as memories as such," but as "fragments of prior events, subjugating the present moment." The traumatic memories appeared to engage a different area of the brain -- the posterior cingulate cortex, or P.C.C., which is usually involved in internally directed thought, like introspection or daydreaming. The more severe the person's PTSD symptoms were, the more activity appeared in the P.C.C. What is striking about this finding is that the P.C.C. is not known as a memory region, but one that is engaged with "processing of internal experience," Dr. Schiller said.

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Brain Study Suggests Traumatic Memories Are Processed as ... - Slashdot

Monoclonal Antibodies Market Size Worth USD 572.62 Billion in … – GlobeNewswire

Vancouver, Nov. 28, 2023 (GLOBE NEWSWIRE) -- The global monoclonal antibodies market size was USD 204.42 billion in 2022 and is expected to register a revenue CAGR of 10.8% during the forecast period. The global monoclonal antibodies market is poised for significant growth, driven by factors such as the rising adoption of personalized medicine, expanding regulatory approvals for monoclonal antibodies, and continuous technological advancements in biotechnology and immunology. These factors, along with the increasing prevalence of cancer and infectious diseases, are contributing to a surge in demand for effective and targeted monoclonal antibody-based therapies. The market witnessed substantial developments in 2022, with major players actively contributing to advancements in monoclonal antibody-based treatments. Notably, GlaxoSmithKline plc. (GSK) and iTeos Therapeutics announced a promising partnership for the development and commercialization of EOS-448, an anti-TIGIT monoclonal antibody, showcasing the potential for next-generation immuno-oncology therapies.

Despite the positive trajectory, challenges such as the impact of the COVID-19 pandemic on manufacturing processes, higher associated manufacturing costs, and a shortage of skilled professionals have hindered revenue growth. Recent safety concerns and FDA cautionary messages regarding specific monoclonal antibodies for COVID-19 treatment, especially in light of the omicron variant, have added complexity to the market dynamics.

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MAJOR COMPANIES and Market Share Analysis

The global monoclonal antibodies market is fairly fragmented, with many large and medium-sized players accounting for the majority of market revenue. Major players are deploying various strategies, entering mergers & acquisitions, strategic agreements & contracts, developing, testing, and introducing more effective monoclonal antibodies solutions. Some major players included in the global monoclonal antibodies market report are:

Strategic Development

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For the purpose of this report, Emergen Research has segmented the global monoclonal antibodies market on the basis of source, indication, production type, end-use, and region:

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Monoclonal Antibodies Market Size Worth USD 572.62 Billion in ... - GlobeNewswire

Nanotechnology In Medicine: Huge Potential, But What Are The Risks?

Nanotechnology, the manipulation of matter at the atomic and molecular scale to create materials with remarkably varied and new properties, is a rapidly expanding area of research with huge potential in many sectors, ranging from healthcare to construction and electronics. In medicine, it promises to revolutionize drug delivery, gene therapy, diagnostics, and many areas of research, development and clinical application.

This article does not attempt to cover the whole field, but offers, by means of some examples, a few insights into how nanotechnology has the potential to change medicine, both in the research lab and clinically, while touching on some of the challenges and concerns that it raises.

The prefix nano stems from the ancient Greek for dwarf. In science it means one billionth (10 to the minus 9) of something, thus a nanometer (nm) is is one billionth of a meter, or 0.000000001 meters. A nanometer is about three to five atoms wide, or some 40,000 times smaller than the thickness of human hair. A virus is typically 100 nm in size.

The ability to manipulate structures and properties at the nanoscale in medicine is like having a sub-microscopic lab bench on which you can handle cell components, viruses or pieces of DNA, using a range of tiny tools, robots and tubes.

Therapies that involve the manipulation of individual genes, or the molecular pathways that influence their expression, are increasingly being investigated as an option for treating diseases. One highly sought goal in this field is the ability to tailor treatments according to the genetic make-up of individual patients.

This creates a need for tools that help scientists experiment and develop such treatments.

Imagine, for example, being able to stretch out a section of DNA like a strand of spaghetti, so you can examine or operate on it, or building nanorobots that can walk and carry out repairs inside cell components. Nanotechnology is bringing that scientific dream closer to reality.

For instance, scientists at the Australian National University have managed to attach coated latex beads to the ends of modified DNA, and then using an optical trap comprising a focused beam of light to hold the beads in place, they have stretched out the DNA strand in order to study the interactions of specific binding proteins.

Meanwhile chemists at New York University (NYU) have created a nanoscale robot from DNA fragments that walks on two legs just 10 nm long. In a 2004 paper published in the journal Nano Letters, they describe how their nanowalker, with the help of psoralen molecules attached to the ends of its feet, takes its first baby steps: two forward and two back.

One of the researchers, Ned Seeman, said he envisages it will be possible to create a molecule-scale production line, where you move a molecule along till the right location is reached, and a nanobot does a bit chemisty on it, rather like spot-welding on a car assembly line. Seemans lab at NYU is also looking to use DNA nanotechnology to make a biochip computer, and to find out how biological molecules crystallize, an area that is currently fraught with challenges.

The work that Seeman and colleagues are doing is a good example of biomimetics, where with nanotechnology they can imitate some of the biological processes in nature, such as the behavior of DNA, to engineer new methods and perhaps even improve them.

DNA-based nanobots are also being created to target cancer cells. For instance, researchers at Harvard Medical School in the US reported recently in Science how they made an origami nanorobot out of DNA to transport a molecular payload. The barrel-shaped nanobot can carry molecules containing instructions that make cells behave in a particular way. In their study, the team successfully demonstrates how it delivered molecules that trigger cell suicide in leukemia and lymphoma cells.

Nanobots made from other materials are also in development. For instance, gold is the material scientists at Northwestern University use to make nanostars, simple, specialized, star-shaped nanoparticles that can href=http://www.medicalnewstoday.com/articles/243856.php>deliver drugs directly to the nuclei of cancer cells. In a recent paper in the journal ACS Nano, they describe how drug-loaded nanostars behave like tiny hitchhikers, that after being attracted to an over-expressed protein on the surface of human cervical and ovarian cancer cells, deposit their payload right into the nuclei of those cells.

The researchers found giving their nanobot the shape of a star helped to overcome one of the challenges of using nanoparticles to deliver drugs: how to release the drugs precisely. They say the shape helps to concentrate the light pulses used to release the drugs precisely at the points of the star.

Scientists are discovering that protein-based drugs are very useful because they can be programmed to deliver specific signals to cells. But the problem with conventional delivery of such drugs is that the body breaks most of them down before they reach their destination.

But what if it were possible to produce such drugs in situ, right at the target site? Well, in a recent issue of Nano Letters, researchers at Massachusetts Institute of Technology (MIT) in the US show how it may be possible to do just that. In their proof of principle study, they demonstrate the feasibility of self-assembling nanofactories that make protein compounds, on demand, at target sites. So far they have tested the idea in mice, by creating nanoparticles programmed to produce either green fluorescent protein (GFP) or luciferase exposed to UV light.

The MIT team came up with the idea while trying to find a way to attack metastatic tumors, those that grow from cancer cells that have migrated from the original site to other parts of the body. Over 90% of cancer deaths are due to metastatic cancer. They are now working on nanoparticles that can synthesize potential cancer drugs, and also on other ways to switch them on.

Nanofibers are fibers with diameters of less than 1,000 nm. Medical applications include special materials for wound dressings and surgical textiles, materials used in implants, tissue engineering and artificial organ components.

Nanofibers made of carbon also hold promise for medical imaging and precise scientific measurement tools. But there are huge challenges to overcome, one of the main ones being how to make them consistently of the correct size. Historically, this has been costly and time-consuming.

But last year, researchers from North Carolina State University, revealed how they had developed a new method for making carbon nanofibers of specific sizes. Writing in ACS Applied Materials & Interfaces in March 2011, they describe how they managed to grow carbon nanofibers uniform in diameter, by using nickel nanoparticles coated with a shell made of ligands, small organic molecules with functional parts that bond directly to metals.

Nickel nanoparticles are particularly interesting because at high temperatures they help grow carbon nanofibers. The researchers also found there was another benefit in using these nanoparticles, they could define where the nanofibers grew and by correct placement of the nanoparticles they could grow the nanofibers in a desired specific pattern: an important feature for useful nanoscale materials.

Lead is another substance that is finding use as a nanofiber, so much so that neurosurgeon-to-be Matthew MacEwan, who is studying at Washington University School of Medicine in St. Louis, started his own nanomedicine company aimed at revolutionizing the surgical mesh that is used in operating theatres worldwide.

The lead product is a synthetic polymer comprising individual strands of nanofibers, and was developed to repair brain and spinal cord injuries, but MacEwan thinks it could also be used to mend hernias, fistulas and other injuries.

Currently, the surgical meshes used to repair the protective membrane that covers the brain and spinal cord are made of thick and stiff material, which is difficult to work with. The lead nanofiber mesh is thinner, more flexible and more likely to integrate with the bodys own tissues, says MacEwan. Every thread of the nanofiber mesh is thousands of times smaller than the diameter of a single cell. The idea is to use the nanofiber material not only to make operations easier for surgeons to carry out, but also so there are fewer post-op complications for patients, because it breaks down naturally over time.

Researchers at the Polytechnic Institute of New York University (NYU-Poly) have recently demonstrated a new way to make nanofibers out of proteins. Writing recently in the journal Advanced Functional Materials, the researchers say they came across their finding almost by chance: they were studying certain cylinder-shaped proteins derived from cartilage, when they noticed that in high concentrations, some of the proteins spontaneously came together and self-assembled into nanofibers.

They carried out further experiments, such as adding metal-recognizing amino acids and different metals, and found they could control fiber formation, alter its shape, and how it bound to small molecules. For instance, adding nickel transformed the fibers into clumped mats, which could be used to trigger the release of an attached drug molecule.

The researchers hope this new method will greatly improve the delivery of drugs to treat cancer, heart disorders and Alzheimers disease. They can also see applications in regeneration of human tissue, bone and cartilage, and even as a way to develop tinier and more powerful microprocessors for use in computers and consumer electronics.

Recent years have seen an explosion in the number of studies showing the variety of medical applications of nanotechnology and nanomaterials. In this article we have glimpsed just a small cross-section of this vast field. However, across the range, there exist considerable challenges, the greatest of which appear to be how to scale up production of materials and tools, and how to bring down costs and timescales.

But another challenge is how to quickly secure public confidence that this rapidly expanding technology is safe. And so far, it is not clear whether that is being done.

There are those who suggest concerns about nanotechnology may be over-exaggerated. They point to the fact that just because a material is nanosized, it does not mean it is dangerous, indeed nanoparticles have been around since the Earth was born, occurring naturally in volcanic ash and sea-spray, for example. As byproducts of human activity, they have been present since the Stone Age, in smoke and soot.

Of attempts to investigate the safety of nanomaterials, the National Cancer Institute in the US says there are so many nanoparticles naturally present in the environment that they are often at order-of-magnitude higher levels than the engineered particles being evaluated. In many respects, they point out, most engineered nanoparticles are far less toxic than household cleaning products, insecticides used on family pets, and over-the-counter dandruff remedies, and that for instance, in their use as carriers of chemotherapeutics in cancer treatment, they are much less toxic than the drugs they carry.

It is perhaps more in the food sector that we have seen some of the greatest expansion of nanomaterials on a commercial level. Although the number of foods that contain nanomaterials is still small, it appears set to change over the next few years as the technology develops. Nanomaterials are already used to lower levels of fat and sugar without altering taste, or to improve packaging to keep food fresher for longer, or to tell consumers if the food is spoiled. They are also being used to increase the bioavailablity of nutrients (for instance in food supplements).

But, there are also concerned parties, who highlight that while the pace of research quickens, and the market for nanomaterials expands, it appears not enough is being done to discover their toxicological consequences.

This was the view of a science and technology committee of the House of Lords of the British Parliament, who in a recent report on nanotechnology and food, raise several concerns about nanomaterials and human health, particularly the risk posed by ingested nanomaterials.

For instance, one area that concerns the committee is the size and exceptional mobility of nanoparticles: they are small enough, if ingested, to penetrate cell membranes of the lining of the gut, with the potential to access the brain and other parts of the body, and even inside the nuclei of cells.

Another is the solubility and persistence of nanomaterials. What happens, for instance, to insoluble nanoparticles? If they cant be broken down and digested or degraded, is there a danger they will accumulate and damage organs? Nanomaterials comprising inorganic metal oxides and metals are thought to be the ones most likely to pose a risk in this area.

Also, because of their high surface area to mass ratio, nanoparticles are highly reactive, and may for instance, trigger as yet unknown chemical reactions, or by bonding with toxins, allow them to enter cells that they would otherwise have no access to.

For instance, with their large surface area, reactivity and electrical charge, nanomaterials create the conditions for what is described as particle aggregation due to physical forces and particle agglomoration due to chemical forces, so that individual nanoparticles come together to form larger ones. This may lead not only to dramatically larger particles, for instance in the gut and inside cells, but could also result in disaggregation of clumps of nanoparticles, which could radically alter their physicochemical properties and chemical reactivity.

Such reversible phenomena add to the difficulty in understanding the behaviour and toxicology of nanomaterials, says the committee, whose overall conclusion is that neither Government nor the Research Councils are giving enough priority to researching the safety of nanotechnology, especially considering the timescale within which products containing nanomaterials may be developed.

They recommend much more research is needed to ensure that regulatory agencies can effectively assess the safety of products before they are allowed onto the market.

It would appear, therefore, whether actual or perceived, the potential risk that nanotechnology poses to human health must be investigated, and be seen to be investigated. Most nanomaterials, as the NCI suggests, will likely prove to be harmless.

But when a technology advances rapidly, knowledge and communication about its safety needs to keep pace in order for it to benefit, especially if it is also to secure public confidence. We only have to look at what happened, and to some extent is still happening, with genetically modified food to see how that can go badly wrong.

Written by Catharine Paddock PhD

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Nanotechnology In Medicine: Huge Potential, But What Are The Risks?

Nanotechnology – Wikipedia

Field of applied science addressing the control of matter on atomic and (supra)molecular scales

Nanotechnology, also shortened to nanotech, is the use of matter on an atomic, molecular, and supramolecular scale for industrial purposes. The earliest, widespread description of nanotechnology referred to the particular technological goal of precisely manipulating atoms and molecules for fabrication of macroscale products, also now referred to as molecular nanotechnology.[1][2] A more generalized description of nanotechnology was subsequently established by the National Nanotechnology Initiative, which defined nanotechnology as the manipulation of matter with at least one dimension sized from 1 to 100 nanometers. This definition reflects the fact that quantum mechanical effects are important at this quantum-realm scale, and so the definition shifted from a particular technological goal to a research category inclusive of all types of research and technologies that deal with the special properties of matter which occur below the given size threshold. It is therefore common to see the plural form "nanotechnologies" as well as "nanoscale technologies" to refer to the broad range of research and applications whose common trait is size.

Nanotechnology as defined by size is naturally broad, including fields of science as diverse as surface science, organic chemistry, molecular biology, semiconductor physics, energy storage,[3][4] engineering,[5] microfabrication,[6] and molecular engineering.[7] The associated research and applications are equally diverse, ranging from extensions of conventional device physics to completely new approaches based upon molecular self-assembly,[8] from developing new materials with dimensions on the nanoscale to direct control of matter on the atomic scale.

Scientists currently debate the future implications of nanotechnology. Nanotechnology may be able to create many new materials and devices with a vast range of applications, such as in nanomedicine, nanoelectronics, biomaterials energy production, and consumer products. On the other hand, nanotechnology raises many of the same issues as any new technology, including concerns about the toxicity and environmental impact of nanomaterials,[9] and their potential effects on global economics, as well as speculation about various doomsday scenarios. These concerns have led to a debate among advocacy groups and governments on whether special regulation of nanotechnology is warranted.

The concepts that seeded nanotechnology were first discussed in 1959 by renowned physicist Richard Feynman in his talk There's Plenty of Room at the Bottom, in which he described the possibility of synthesis via direct manipulation of atoms.

The term "nano-technology" was first used by Norio Taniguchi in 1974, though it was not widely known. Inspired by Feynman's concepts, K. Eric Drexler used the term "nanotechnology" in his 1986 book Engines of Creation: The Coming Era of Nanotechnology, which proposed the idea of a nanoscale "assembler" which would be able to build a copy of itself and of other items of arbitrary complexity with atomic control. Also in 1986, Drexler co-founded The Foresight Institute (with which he is no longer affiliated) to help increase public awareness and understanding of nanotechnology concepts and implications.

The emergence of nanotechnology as a field in the 1980s occurred through convergence of Drexler's theoretical and public work, which developed and popularized a conceptual framework for nanotechnology, and high-visibility experimental advances that drew additional wide-scale attention to the prospects of atomic control of matter. In the 1980s, two major breakthroughs sparked the growth of nanotechnology in the modern era. First, the invention of the scanning tunneling microscope in 1981 which provided unprecedented visualization of individual atoms and bonds, and was successfully used to manipulate individual atoms in 1989. The microscope's developers Gerd Binnig and Heinrich Rohrer at IBM Zurich Research Laboratory received a Nobel Prize in Physics in 1986.[10][11] Binnig, Quate and Gerber also invented the analogous atomic force microscope that year.

Second, fullerenes were discovered in 1985 by Harry Kroto, Richard Smalley, and Robert Curl, who together won the 1996 Nobel Prize in Chemistry.[12][13] C60 was not initially described as nanotechnology; the term was used regarding subsequent work with related carbon nanotubes (sometimes called graphene tubes or Bucky tubes) which suggested potential applications for nanoscale electronics and devices. The discovery of carbon nanotubes is largely attributed to Sumio Iijima of NEC in 1991,[14] for which Iijima won the inaugural 2008 Kavli Prize in Nanoscience.

A nanolayer-base metalsemiconductor junction (MS junction) transistor was initially proposed by A. Rose in 1960, and fabricated by L. Geppert, Mohamed Atalla and Dawon Kahng in 1962.[15] Decades later, advances in multi-gate technology enabled the scaling of metaloxidesemiconductor field-effect transistor (MOSFET) devices down to nano-scale levels smaller than 20nm gate length, starting with the FinFET (fin field-effect transistor), a three-dimensional, non-planar, double-gate MOSFET. At UC Berkeley, a team of researchers including Digh Hisamoto, Chenming Hu, Tsu-Jae King Liu, Jeffrey Bokor and others fabricated FinFET devices down to a 17nm process in 1998, then 15nm in 2001, and then 10nm in 2002.[16]

In the early 2000s, the field garnered increased scientific, political, and commercial attention that led to both controversy and progress. Controversies emerged regarding the definitions and potential implications of nanotechnologies, exemplified by the Royal Society's report on nanotechnology.[17] Challenges were raised regarding the feasibility of applications envisioned by advocates of molecular nanotechnology, which culminated in a public debate between Drexler and Smalley in 2001 and 2003.[18]

Meanwhile, commercialization of products based on advancements in nanoscale technologies began emerging. These products are limited to bulk applications of nanomaterials and do not involve atomic control of matter. Some examples include the Silver Nano platform for using silver nanoparticles as an antibacterial agent, nanoparticle-based transparent sunscreens, carbon fiber strengthening using silica nanoparticles, and carbon nanotubes for stain-resistant textiles.[19][20]

Governments moved to promote and fund research into nanotechnology, such as in the U.S. with the National Nanotechnology Initiative, which formalized a size-based definition of nanotechnology and established funding for research on the nanoscale, and in Europe via the European Framework Programmes for Research and Technological Development.

By the mid-2000s new and serious scientific attention began to flourish. Projects emerged to produce nanotechnology roadmaps[21][22] which center on atomically precise manipulation of matter and discuss existing and projected capabilities, goals, and applications.

In 2006, a team of Korean researchers from the Korea Advanced Institute of Science and Technology (KAIST) and the National Nano Fab Center developed a 3nm MOSFET, the world's smallest nanoelectronic device. It was based on gate-all-around (GAA) FinFET technology.[23][24]

Over sixty countries created nanotechnology research and development (R&D) government programs between 2001 and 2004. Government funding was exceeded by corporate spending on nanotechnology R&D, with most of the funding coming from corporations based in the United States, Japan and Germany. The top five organizations that filed the most intellectual patents on nanotechnology R&D between 1970 and 2011 were Samsung Electronics (2,578 first patents), Nippon Steel (1,490 first patents), IBM (1,360 first patents), Toshiba (1,298 first patents) and Canon (1,162 first patents). The top five organizations that published the most scientific papers on nanotechnology research between 1970 and 2012 were the Chinese Academy of Sciences, Russian Academy of Sciences, Centre national de la recherche scientifique, University of Tokyo and Osaka University.[25]

Nanotechnology is the engineering of functional systems at the molecular scale. This covers both current work and concepts that are more advanced. In its original sense, nanotechnology refers to the projected ability to construct items from the bottom up, using techniques and tools being developed today to make complete, high-performance products.

One nanometer (nm) is one billionth, or 109, of a meter. By comparison, typical carbon-carbon bond lengths, or the spacing between these atoms in a molecule, are in the range 0.120.15 nm, and a DNA double-helix has a diameter around 2nm. On the other hand, the smallest cellular life-forms, the bacteria of the genus Mycoplasma, are around 200nm in length. By convention, nanotechnology is taken as the scale range 1 to 100 nm following the definition used by the National Nanotechnology Initiative in the US. The lower limit is set by the size of atoms (hydrogen has the smallest atoms, which are approximately a quarter of a nm kinetic diameter) since nanotechnology must build its devices from atoms and molecules. The upper limit is more or less arbitrary but is around the size below which the phenomena not observed in larger structures start to become apparent and can be made use of in the nano device.[26] These new phenomena make nanotechnology distinct from devices which are merely miniaturised versions of an equivalent macroscopic device; such devices are on a larger scale and come under the description of microtechnology.[27]

To put that scale in another context, the comparative size of a nanometer to a meter is the same as that of a marble to the size of the earth.[28] Or another way of putting it: a nanometer is the amount an average man's beard grows in the time it takes him to raise the razor to his face.[28]

Two main approaches are used in nanotechnology. In the "bottom-up" approach, materials and devices are built from molecular components which assemble themselves chemically by principles of molecular recognition.[29] In the "top-down" approach, nano-objects are constructed from larger entities without atomic-level control.[30]

Areas of physics such as nanoelectronics, nanomechanics, nanophotonics and nanoionics have evolved during the last few decades to provide a basic scientific foundation of nanotechnology.

Several phenomena become pronounced as the size of the system decreases. These include statistical mechanical effects, as well as quantum mechanical effects, for example the "quantum size effect" where the electronic properties of solids are altered with great reductions in particle size. This effect does not come into play by going from macro to micro dimensions. However, quantum effects can become significant when the nanometer size range is reached, typically at distances of 100 nanometers or less, the so-called quantum realm. Additionally, a number of physical (mechanical, electrical, optical, etc.) properties change when compared to macroscopic systems. One example is the increase in surface area to volume ratio altering mechanical, thermal and catalytic properties of materials. Diffusion and reactions at nanoscale, nanostructures materials and nanodevices with fast ion transport are generally referred to nanoionics. Mechanical properties of nanosystems are of interest in the nanomechanics research. The catalytic activity of nanomaterials also opens potential risks in their interaction with biomaterials.

Materials reduced to the nanoscale can show different properties compared to what they exhibit on a macroscale, enabling unique applications. For instance, opaque substances can become transparent (copper); stable materials can turn combustible (aluminium); insoluble materials may become soluble (gold). A material such as gold, which is chemically inert at normal scales, can serve as a potent chemical catalyst at nanoscales. Much of the fascination with nanotechnology stems from these quantum and surface phenomena that matter exhibits at the nanoscale.[31]

Modern synthetic chemistry has reached the point where it is possible to prepare small molecules to almost any structure. These methods are used today to manufacture a wide variety of useful chemicals such as pharmaceuticals or commercial polymers. This ability raises the question of extending this kind of control to the next-larger level, seeking methods to assemble these single molecules into supramolecular assemblies consisting of many molecules arranged in a well defined manner.

These approaches utilize the concepts of molecular self-assembly and/or supramolecular chemistry to automatically arrange themselves into some useful conformation through a bottom-up approach. The concept of molecular recognition is especially important: molecules can be designed so that a specific configuration or arrangement is favored due to non-covalent intermolecular forces. The WatsonCrick basepairing rules are a direct result of this, as is the specificity of an enzyme being targeted to a single substrate, or the specific folding of the protein itself. Thus, two or more components can be designed to be complementary and mutually attractive so that they make a more complex and useful whole.

Such bottom-up approaches should be capable of producing devices in parallel and be much cheaper than top-down methods, but could potentially be overwhelmed as the size and complexity of the desired assembly increases. Most useful structures require complex and thermodynamically unlikely arrangements of atoms. Nevertheless, there are many examples of self-assembly based on molecular recognition in biology, most notably WatsonCrick basepairing and enzyme-substrate interactions. The challenge for nanotechnology is whether these principles can be used to engineer new constructs in addition to natural ones.

Molecular nanotechnology, sometimes called molecular manufacturing, describes engineered nanosystems (nanoscale machines) operating on the molecular scale. Molecular nanotechnology is especially associated with the molecular assembler, a machine that can produce a desired structure or device atom-by-atom using the principles of mechanosynthesis. Manufacturing in the context of productive nanosystems is not related to, and should be clearly distinguished from, the conventional technologies used to manufacture nanomaterials such as carbon nanotubes and nanoparticles.

When the term "nanotechnology" was independently coined and popularized by Eric Drexler (who at the time was unaware of an earlier usage by Norio Taniguchi) it referred to a future manufacturing technology based on molecular machine systems. The premise was that molecular-scale biological analogies of traditional machine components demonstrated molecular machines were possible: by the countless examples found in biology, it is known that sophisticated, stochastically optimized biological machines can be produced.

It is hoped that developments in nanotechnology will make possible their construction by some other means, perhaps using biomimetic principles. However, Drexler and other researchers[32] have proposed that advanced nanotechnology, although perhaps initially implemented by biomimetic means, ultimately could be based on mechanical engineering principles, namely, a manufacturing technology based on the mechanical functionality of these components (such as gears, bearings, motors, and structural members) that would enable programmable, positional assembly to atomic specification.[33] The physics and engineering performance of exemplar designs were analyzed in Drexler's book Nanosystems.

In general it is very difficult to assemble devices on the atomic scale, as one has to position atoms on other atoms of comparable size and stickiness. Another view, put forth by Carlo Montemagno,[34] is that future nanosystems will be hybrids of silicon technology and biological molecular machines. Richard Smalley argued that mechanosynthesis are impossible due to the difficulties in mechanically manipulating individual molecules.

This led to an exchange of letters in the ACS publication Chemical & Engineering News in 2003.[35] Though biology clearly demonstrates that molecular machine systems are possible, non-biological molecular machines are today only in their infancy. Leaders in research on non-biological molecular machines are Dr. Alex Zettl and his colleagues at Lawrence Berkeley Laboratories and UC Berkeley.[1] They have constructed at least three distinct molecular devices whose motion is controlled from the desktop with changing voltage: a nanotube nanomotor, a molecular actuator,[36] and a nanoelectromechanical relaxation oscillator.[37] See nanotube nanomotor for more examples.

An experiment indicating that positional molecular assembly is possible was performed by Ho and Lee at Cornell University in 1999. They used a scanning tunneling microscope to move an individual carbon monoxide molecule (CO) to an individual iron atom (Fe) sitting on a flat silver crystal, and chemically bound the CO to the Fe by applying a voltage.

The nanomaterials field includes subfields which develop or study materials having unique properties arising from their nanoscale dimensions.[40]

These seek to arrange smaller components into more complex assemblies.

These seek to create smaller devices by using larger ones to direct their assembly.

These seek to develop components of a desired functionality without regard to how they might be assembled.

These subfields seek to anticipate what inventions nanotechnology might yield, or attempt to propose an agenda along which inquiry might progress. These often take a big-picture view of nanotechnology, with more emphasis on its societal implications than the details of how such inventions could actually be created.

Nanomaterials can be classified in 0D, 1D, 2D and 3D nanomaterials. The dimensionality play a major role in determining the characteristic of nanomaterials including physical, chemical and biological characteristics. With the decrease in dimensionality, an increase in surface-to-volume ratio is observed. This indicate that smaller dimensional nanomaterials have higher surface area compared to 3D nanomaterials. Recently, two dimensional (2D) nanomaterials are extensively investigated for electronic, biomedical, drug delivery and biosensor applications.

There are several important modern developments. The atomic force microscope (AFM) and the Scanning Tunneling Microscope (STM) are two early versions of scanning probes that launched nanotechnology. There are other types of scanning probe microscopy. Although conceptually similar to the scanning confocal microscope developed by Marvin Minsky in 1961 and the scanning acoustic microscope (SAM) developed by Calvin Quate and coworkers in the 1970s, newer scanning probe microscopes have much higher resolution, since they are not limited by the wavelength of sound or light.

The tip of a scanning probe can also be used to manipulate nanostructures (a process called positional assembly). Feature-oriented scanning methodology may be a promising way to implement these nanomanipulations in automatic mode.[57][58] However, this is still a slow process because of low scanning velocity of the microscope.

Various techniques of nanolithography such as optical lithography, X-ray lithography, dip pen nanolithography, electron beam lithography or nanoimprint lithography were also developed. Lithography is a top-down fabrication technique where a bulk material is reduced in size to nanoscale pattern.

Another group of nanotechnological techniques include those used for fabrication of nanotubes and nanowires, those used in semiconductor fabrication such as deep ultraviolet lithography, electron beam lithography, focused ion beam machining, nanoimprint lithography, atomic layer deposition, and molecular vapor deposition, and further including molecular self-assembly techniques such as those employing di-block copolymers. The precursors of these techniques preceded the nanotech era, and are extensions in the development of scientific advancements rather than techniques which were devised with the sole purpose of creating nanotechnology and which were results of nanotechnology research.[59]

The top-down approach anticipates nanodevices that must be built piece by piece in stages, much as manufactured items are made. Scanning probe microscopy is an important technique both for characterization and synthesis of nanomaterials. Atomic force microscopes and scanning tunneling microscopes can be used to look at surfaces and to move atoms around. By designing different tips for these microscopes, they can be used for carving out structures on surfaces and to help guide self-assembling structures. By using, for example, feature-oriented scanning approach, atoms or molecules can be moved around on a surface with scanning probe microscopy techniques.[57][58] At present, it is expensive and time-consuming for mass production but very suitable for laboratory experimentation.

In contrast, bottom-up techniques build or grow larger structures atom by atom or molecule by molecule. These techniques include chemical synthesis, self-assembly and positional assembly. Dual polarisation interferometry is one tool suitable for characterisation of self assembled thin films. Another variation of the bottom-up approach is molecular beam epitaxy or MBE. Researchers at Bell Telephone Laboratories like John R. Arthur. Alfred Y. Cho, and Art C. Gossard developed and implemented MBE as a research tool in the late 1960s and 1970s. Samples made by MBE were key to the discovery of the fractional quantum Hall effect for which the 1998 Nobel Prize in Physics was awarded. MBE allows scientists to lay down atomically precise layers of atoms and, in the process, build up complex structures. Important for research on semiconductors, MBE is also widely used to make samples and devices for the newly emerging field of spintronics.

However, new therapeutic products, based on responsive nanomaterials, such as the ultradeformable, stress-sensitive Transfersome vesicles, are under development and already approved for human use in some countries.[60]

Because of the variety of potential applications (including industrial and military), governments have invested billions of dollars in nanotechnology research. Prior to 2012, the USA invested $3.7 billion using its National Nanotechnology Initiative, the European Union invested $1.2 billion, and Japan invested $750 million.[61] Over sixty countries created nanotechnology research and development (R&D) programs between 2001 and 2004. In 2012, the US and EU each invested $2.1 billion on nanotechnology research, followed by Japan with $1.2 billion. Global investment reached $7.9 billion in 2012. Government funding was exceeded by corporate R&D spending on nanotechnology research, which was $10 billion in 2012. The largest corporate R&D spenders were from the US, Japan and Germany which accounted for a combined $7.1 billion.[25]

As of August 21, 2008, the Project on Emerging Nanotechnologies estimates that over 800 manufacturer-identified nanotech products are publicly available, with new ones hitting the market at a pace of 34 per week.[20] The project lists all of the products in a publicly accessible online database. Most applications are limited to the use of "first generation" passive nanomaterials which includes titanium dioxide in sunscreen, cosmetics, surface coatings,[62] and some food products; Carbon allotropes used to produce gecko tape; silver in food packaging, clothing, disinfectants and household appliances; zinc oxide in sunscreens and cosmetics, surface coatings, paints and outdoor furniture varnishes; and cerium oxide as a fuel catalyst.[19]

Further applications allow tennis balls to last longer, golf balls to fly straighter, and even bowling balls to become more durable and have a harder surface. Trousers and socks have been infused with nanotechnology so that they will last longer and keep people cool in the summer. Bandages are being infused with silver nanoparticles to heal cuts faster.[63] Video game consoles and personal computers may become cheaper, faster, and contain more memory thanks to nanotechnology.[64] Also, to build structures for on chip computing with light, for example on chip optical quantum information processing, and picosecond transmission of information.[65]

Nanotechnology may have the ability to make existing medical applications cheaper and easier to use in places like the general practitioner's office and at home.[66] Cars are being manufactured with nanomaterials so they may need fewer metals and less fuel to operate in the future.[67]

Scientists are now turning to nanotechnology in an attempt to develop diesel engines with cleaner exhaust fumes. Platinum is currently used as the diesel engine catalyst in these engines. The catalyst is what cleans the exhaust fume particles. First a reduction catalyst is employed to take nitrogen atoms from NOx molecules in order to free oxygen. Next the oxidation catalyst oxidizes the hydrocarbons and carbon monoxide to form carbon dioxide and water.[68] Platinum is used in both the reduction and the oxidation catalysts.[69] Using platinum though, is inefficient in that it is expensive and unsustainable. Danish company InnovationsFonden invested DKK 15 million in a search for new catalyst substitutes using nanotechnology. The goal of the project, launched in the autumn of 2014, is to maximize surface area and minimize the amount of material required. Objects tend to minimize their surface energy; two drops of water, for example, will join to form one drop and decrease surface area. If the catalyst's surface area that is exposed to the exhaust fumes is maximized, efficiency of the catalyst is maximized. The team working on this project aims to create nanoparticles that will not merge. Every time the surface is optimized, material is saved. Thus, creating these nanoparticles will increase the effectiveness of the resulting diesel engine catalystin turn leading to cleaner exhaust fumesand will decrease cost. If successful, the team hopes to reduce platinum use by 25%.[70]

Nanotechnology also has a prominent role in the fast developing field of Tissue Engineering. When designing scaffolds, researchers attempt to mimic the nanoscale features of a cell's microenvironment to direct its differentiation down a suitable lineage.[71] For example, when creating scaffolds to support the growth of bone, researchers may mimic osteoclast resorption pits.[72]

Researchers have successfully used DNA origami-based nanobots capable of carrying out logic functions to achieve targeted drug delivery in cockroaches. It is said that the computational power of these nanobots can be scaled up to that of a Commodore 64.[73]

Commercial nanoelectronic semiconductor device fabrication began in the 2010s. In 2013, SK Hynix began commercial mass-production of a 16nm process,[74] TSMC began production of a 16nm FinFET process,[75] and Samsung Electronics began production of a 10nm process.[76] TSMC began production of a 7nm process in 2017,[77] and Samsung began production of a 5nm process in 2018.[78] In 2019, Samsung announced plans for the commercial production of a 3nm GAAFET process by 2021.[79]

Commercial production of nanoelectronic semiconductor memory also began in the 2010s. In 2013, SK Hynix began mass-production of 16nm NAND flash memory,[74] and Samsung began production of 10nm multi-level cell (MLC) NAND flash memory.[76] In 2017, TSMC began production of SRAM memory using a 7nm process.[77]

An area of concern is the effect that industrial-scale manufacturing and use of nanomaterials would have on human health and the environment, as suggested by nanotoxicology research. For these reasons, some groups advocate that nanotechnology be regulated by governments. Others counter that overregulation would stifle scientific research and the development of beneficial innovations. Public health research agencies, such as the National Institute for Occupational Safety and Health are actively conducting research on potential health effects stemming from exposures to nanoparticles.[80][81]

Some nanoparticle products may have unintended consequences. Researchers have discovered that bacteriostatic silver nanoparticles used in socks to reduce foot odor are being released in the wash.[82] These particles are then flushed into the waste water stream and may destroy bacteria which are critical components of natural ecosystems, farms, and waste treatment processes.[83]

Public deliberations on risk perception in the US and UK carried out by the Center for Nanotechnology in Society found that participants were more positive about nanotechnologies for energy applications than for health applications, with health applications raising moral and ethical dilemmas such as cost and availability.[84]

Experts, including director of the Woodrow Wilson Center's Project on Emerging Nanotechnologies David Rejeski, have testified[85] that successful commercialization depends on adequate oversight, risk research strategy, and public engagement. Berkeley, California is currently the only city in the United States to regulate nanotechnology;[86] Cambridge, Massachusetts in 2008 considered enacting a similar law,[87] but ultimately rejected it.[88]

Nanofibers are used in several areas and in different products, in everything from aircraft wings to tennis rackets. Inhaling airborne nanoparticles and nanofibers may lead to a number of pulmonary diseases, e.g. fibrosis.[89] Researchers have found that when rats breathed in nanoparticles, the particles settled in the brain and lungs, which led to significant increases in biomarkers for inflammation and stress response[90] and that nanoparticles induce skin aging through oxidative stress in hairless mice.[91][92]

A two-year study at UCLA's School of Public Health found lab mice consuming nano-titanium dioxide showed DNA and chromosome damage to a degree "linked to all the big killers of man, namely cancer, heart disease, neurological disease and aging".[93]

A Nature Nanotechnology study suggests some forms of carbon nanotubes a poster child for the "nanotechnology revolution" could be as harmful as asbestos if inhaled in sufficient quantities. Anthony Seaton of the Institute of Occupational Medicine in Edinburgh, Scotland, who contributed to the article on carbon nanotubes said "We know that some of them probably have the potential to cause mesothelioma. So those sorts of materials need to be handled very carefully."[94] In the absence of specific regulation forthcoming from governments, Paull and Lyons (2008) have called for an exclusion of engineered nanoparticles in food.[95] A newspaper article reports that workers in a paint factory developed serious lung disease and nanoparticles were found in their lungs.[96][97][98][99]

Calls for tighter regulation of nanotechnology have occurred alongside a growing debate related to the human health and safety risks of nanotechnology.[100] There is significant debate about who is responsible for the regulation of nanotechnology. Some regulatory agencies currently cover some nanotechnology products and processes (to varying degrees) by "bolting on" nanotechnology to existing regulations there are clear gaps in these regimes.[101] Davies (2008) has proposed a regulatory road map describing steps to deal with these shortcomings.[102]

Stakeholders concerned by the lack of a regulatory framework to assess and control risks associated with the release of nanoparticles and nanotubes have drawn parallels with bovine spongiform encephalopathy ("mad cow" disease), thalidomide, genetically modified food,[103] nuclear energy, reproductive technologies, biotechnology, and asbestosis. Dr. Andrew Maynard, chief science advisor to the Woodrow Wilson Center's Project on Emerging Nanotechnologies, concludes that there is insufficient funding for human health and safety research, and as a result there is currently limited understanding of the human health and safety risks associated with nanotechnology.[104] As a result, some academics have called for stricter application of the precautionary principle, with delayed marketing approval, enhanced labelling and additional safety data development requirements in relation to certain forms of nanotechnology.[105]

The Royal Society report[17] identified a risk of nanoparticles or nanotubes being released during disposal, destruction and recycling, and recommended that "manufacturers of products that fall under extended producer responsibility regimes such as end-of-life regulations publish procedures outlining how these materials will be managed to minimize possible human and environmental exposure" (p. xiii).

The Center for Nanotechnology in Society has found that people respond to nanotechnologies differently, depending on application with participants in public deliberations more positive about nanotechnologies for energy than health applications suggesting that any public calls for nano regulations may differ by technology sector.[84]

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Nanotechnology - Wikipedia

Applications of Nanotechnology – National Nanotechnology Initiative

After more than 20 years of basic nanoscience research andmore than fifteen years of focused R&D under the NNI, applications of nanotechnology are delivering in both expected and unexpected ways on nanotechnologys promise to benefit society.

Nanotechnology is helping to considerably improve, even revolutionize, many technology and industry sectors: information technology, homeland security, medicine, transportation, energy, food safety, and environmental science, among many others. Described below is a sampling of the rapidly growing list of benefits and applications of nanotechnology.

Many benefits of nanotechnology depend on the fact that it is possible to tailor the structures of materials at extremely small scales to achieve specific properties, thus greatly extending the materials science toolkit. Using nanotechnology, materials can effectively be made stronger, lighter, more durable, more reactive, more sieve-like, or better electrical conductors, among many other traits. Many everyday commercial products are currently on the market and in daily use that rely on nanoscale materials and processes:

Nanotechnology has greatly contributed to major advances in computing and electronics, leading to faster, smaller, and more portable systems that can manage and store larger and larger amounts of information. These continuously evolving applications include:

Nanotechnology is already broadening the medical tools, knowledge, and therapies currently available to clinicians. Nanomedicine, the application of nanotechnology in medicine, draws on the natural scale of biological phenomena to produce precise solutions for disease prevention, diagnosis, and treatment. Below are some examples of recent advances in this area:

Nanotechnology is finding application in traditional energy sources and is greatly enhancing alternative energy approaches to help meet the worlds increasing energy demands. Many scientists are looking into ways to develop clean, affordable, and renewable energy sources, along with means to reduce energy consumption and lessen toxicity burdens on the environment:

In addition to the ways that nanotechnology can help improve energy efficiency (see the section above), there are also many ways that it can help detect and clean up environmental contaminants:

Nanotechnology offers the promise of developing multifunctional materials that will contribute to building and maintaining lighter, safer, smarter, and more efficient vehicles, aircraft, spacecraft, and ships. In addition, nanotechnology offers various means to improve the transportation infrastructure:

Please visit the Environmental, Health, and Safety Issues and the Ethical, Legal, and Societal Issues pages on nano.gov to learn more about how the National Nanotechnology Initiative is committed to responsibly addressing these issues.

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Applications of Nanotechnology - National Nanotechnology Initiative

Pulse Biosciences Announces FDA 510(k) Clearance for the Treatment of Sebaceous Hyperplasia – Business Wire

HAYWARD, Calif.--(BUSINESS WIRE)--Pulse Biosciences, Inc. (Nasdaq: PLSE), a novel bioelectric medicine company developing the CellFX System powered by Nano-Pulse Stimulation (NPS) technology, today announced receipt of U.S. Food and Drug Administration (FDA) 510(k) clearance for its CellFX System, expanding the indication for use to include the treatment of sebaceous hyperplasia in patients with Fitzpatrick skin types I-III. This specific indication clearance enhances the CellFX Systems general indication FDA clearance and enables the Company to support clinics in marketing and promoting CellFX treatments specifically for patients with sebaceous hyperplasia. The clearance was based on clinical data from the Companys IDE approved study for the treatment of sebaceous hyperplasia.

The Company also recently received FDA 510(k) clearance of two additional treatment tips with larger spot sizes, specifically 7.5mm and 10mm tip sizes, for treating larger benign lesions. These treatment tips broaden the portfolio of previously available 1.5mm, 2.5mm and 5.0mm treatment tip sizes.

We are pleased with the continued advancement of the CellFX System and its capabilities to enhance its value proposition for patients, clinicians and any potential commercial partner. These clearances provide further validation of the systems strong safety and effectiveness profile, said Kevin Danahy, President and Chief Executive Officer of Pulse Biosciences. We would like to thank all of the investigators, the staff at their clinics and the patients who participated in these trials, as well as the FDA for their ongoing collaboration as we endeavor to offer the benefits of NPS technology to more patients.

About Pulse Biosciences

Pulse Biosciences is a novel bioelectric medicine company committed to health innovation that has the potential to improve the quality of life for patients. The Companys proprietary Nano-Pulse Stimulation technology delivers nano-second pulses of electrical energy to non-thermally clear cells while sparing adjacent non-cellular tissue. The CellFX System is the first commercial product to harness the distinctive advantages of NPS technology to treat a variety of conditions for which an optimal solution remains unfulfilled. The Company is actively pursuing application development in cardiology, oncology, gastroenterology, and other medical specialties. Designed as a multi-application platform, the CellFX System offers customer value with a utilization-based revenue model. Visit http://www.pulsebiosciences.com to learn more.

Pulse Biosciences, CellFX, Nano-Pulse Stimulation, NPS, and the stylized logos are among the trademarks and/or registered trademarks of Pulse Biosciences, Inc. in the United States and other countries.

Forward-Looking Statements

All statements in this press release that are not historical are forward-looking statements, including, among other things, statements relating to Pulse Biosciences expectations concerning customer adoption and future use of the CellFX System to address a range of dermatologic conditions, statements relating to the Companys future product development in healthcare outside of dermatology and the Companys other activities to develop and commercialize NPS technology to drive growth, statements about the Companys ability to pursue and complete strategic transactions and its prospects to partner any of its programs, whether in dermatology or otherwise, statements relating to the effectiveness of the Companys NPS technology and the CellFX System to improve the quality of life for patients, and Pulse Biosciences expectations, whether stated or implied, regarding whether any regulatory clearances will enhance the value proposition of the CellFX System for patients, clinicians or others, and other future events. These statements are not historical facts but rather are based on Pulse Biosciences current expectations, estimates, and projections regarding Pulse Biosciences business, operations and other similar or related factors. Words such as may, will, could, would, should, anticipate, predict, potential, continue, expects, intends, plans, projects, believes, estimates, and other similar or related expressions are used to identify these forward-looking statements, although not all forward-looking statements contain these words. You should not place undue reliance on forward-looking statements because they involve known and unknown risks, uncertainties, and assumptions that are difficult or impossible to predict and, in some cases, beyond Pulse Biosciences control. Actual results may differ materially from those in the forward-looking statements as a result of a number of factors, including those described in Pulse Biosciences filings with the Securities and Exchange Commission. Pulse Biosciences undertakes no obligation to revise or update information in this release to reflect events or circumstances in the future, even if new information becomes available.

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Pulse Biosciences Announces FDA 510(k) Clearance for the Treatment of Sebaceous Hyperplasia - Business Wire

Clene to Report HEALEY ALS Platform Trial Topline Results on Monday, October 3 – Investing News Network

As announced in February 2022, the trial was stopped prematurely due to COVID-19 pandemic operational challenges, limiting enrollment to 73 out of the 150 planned participants. Due to the limited enrollment, the threshold for significance was pre-specified at p=0.10 prior to database lock. The primary analysis was conducted in a modified intent to treat (mITT) population, which censored invalid data. The mITT population excluded data from a single site (n=9) with LCLA testing execution errors and the timed 25-foot walk data from one subject with a change in mobility assist device. The ITT results were directionally consistent with the mITT results, although the ITT results were not significant.

"These data are very encouraging to us in the MS research and treatment community as we work to address functional improvement in patients," said Benjamin Greenberg, MD, MHS, FANA, FAAN, CRND Professor of Neurology and one of the trial's clinical advisors. "The MS community has been successful at limiting relapses, but we need therapies to address progression independent of relapse activity (PIRA). This study was designed as a proof-of-concept evaluation to establish that treatment of neuronal and glial energetic failure can support remyelination and neuroprotection in people living with MS. I am pleased to see the potential effectiveness of CNM-Au8 demonstrated in this trial."

Primary and secondary results from Baseline to Week 48 were:

Consistent improvements favoring CNM-Au8 were observed across multiple paraclinical biomarkers, including multifocal visual evoked potentials (mfVEP) amplitude and latency, optical coherence tomography (OCT), and MRI endpoints, including magnetization transfer ratio and diffusion tensor imaging metrics. Placebo treated patients, in contrast, generally worsened as expected across these measures during the 48-week period. These data provide independently assessed quantitative physiological evidence that supports the potential neuroprotective and remyelinating effects of CNM-Au8. The full dataset will be reported at an upcoming scientific congress.

CNM-Au8 was well-tolerated, and there were no significant safety findings reported.

Robert Glanzman, MD, FAAN, Clene's Chief Medical Officer, said, "In this study, CNM-Au8 demonstrated neurological improvements in people with stable relapsing MS as adjunctive therapy to immunomodulatory DMTs. I am very impressed by the consistency of structural and functional improvements demonstrated by CNM-Au8 throughout the neuraxis. With these data, Clene looks forward to initiating a Phase 3 clinical program in people with MS who are experiencing progression independent of relapse activity, the most urgent unmet medical need in MS today. We look forward to the next phase of clinical development."

Rob Etherington, Clene's Chief Executive Officer and President, added, "These results further demonstrate the potential of CNM-Au8 to drive neuronal cellular energy production in patients struggling with MS and other neurodegenerative diseases. We also await additional evidence of clinical efficacy from the HEALEY ALS Platform Trial, which is expected to report topline data later in this quarter. Clene will continue to work tirelessly to further CNM-Au8's development to treat neurodegenerative diseases."

Conference Call and Webcast Information Clene will host a conference call and webcast at 7:30 am EDT to discuss the VISIONARY-MS topline results.

Toll free: 1 (888) 770-7152 Conference ID: 5318408 Press *1 to ask or withdraw a question, or *0 for operator assistance .

To access the live webcast, please register online at this link . Participants are requested to register at a minimum 15 minutes before the start of the call. A replay of the call will be available two hours after the call and archived on the same web page for six months. A live audio webcast of the call will be available on the Investors section of the Company's website Presentation page . An archived webcast will be available on the Company's website approximately two hours after the event.

About VISIONARY-MS VISIONARY-MS was a Phase 2 multi-center, randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of CNM-Au8 in participants with stable relapsing remitting multiple sclerosis (RRMS) with a history of chronic visual impairment who are allowed disease-modifying therapy (DMT). Enrolled subjects were randomized 1:1:1 to CNM-Au8 15 mg/day, 30 mg/day, or placebo. As announced in February 2022, the trial was stopped prematurely due to COVID-19 pandemic operational challenges, enrolling 73 out of the 150 planned participants. Due to limited enrollment, the threshold for significance was pre-specified at p=0.10 prior to database lock. The primary endpoint was the change in best corrected-low contrast letter acuity (BC-LCLA) from baseline to week 48 in the clinically affected eye. Key secondary efficacy outcomes assessed neurological function by the modified MS Functional Composite (mMSFC) including 25-Foot Timed Walk, Symbol Digit Modalities Test, 9-Hole Peg Test (dominant and non-dominant hands), and LCLA (affected and fellow eye) from baseline through Week 48. For more information, see ClinicalTrials.gov . Identifier: NCT03536559 . The open label extension of VISIONARY-MS is ongoing.

About CNM-Au8 CNM-Au8 is an oral suspension of gold nanocrystals developed to restore neuronal health and function by increasing energy production and utilization. The catalytically active nanocrystals of CNM-Au8 drive critical cellular energy producing reactions that enable neuroprotection and remyelination by increasing neuronal and glial resilience to disease-relevant stressors. CNM-Au8 is a federally registered trademark of Clene Nanomedicine, Inc.

About Clene Clene is a clinical-stage biopharmaceutical company focused on revolutionizing the treatment of neurodegenerative disease by targeting energetic failure, an underlying cause of many neurological diseases. The company is based in Salt Lake City, Utah, with R&D and manufacturing operations in Maryland. For more information, please visit http://www.clene.com or follow us on Twitter , LinkedIn and Facebook .

Forward-Looking Statements

This press release contains "forward-looking statements" within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and Section 27A of the Securities Act of 1933, as amended, which are intended to be covered by the "safe harbor" provisions created by those laws. Clene's forward-looking statements include, but are not limited to, statements regarding our or our management team's expectations, hopes, beliefs, intentions or strategies regarding our future operations. In addition, any statements that refer to projections, forecasts or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking statements. The words "anticipate," "believe," "contemplate," "continue," "estimate," "expect," "intends," "may," "might," "plan," "possible," "potential," "predict," "project," "should," "will," "would," and similar expressions may identify forward-looking statements, but the absence of these words does not mean that a statement is not forward-looking. These forward-looking statements represent our views as of the date of this press release and involve a number of judgments, risks and uncertainties. We anticipate that subsequent events and developments will cause our views to change. We undertake no obligation to update forward-looking statements to reflect events or circumstances after the date they were made, whether as a result of new information, future events or otherwise, except as may be required under applicable securities laws. Accordingly, forward-looking statements should not be relied upon as representing our views as of any subsequent date. As a result of a number of known and unknown risks and uncertainties, our actual results or performance may be materially different from those expressed or implied by these forward-looking statements. Some factors that could cause actual results to differ include our ability to demonstrate the efficacy and safety of our drug candidates; the clinical results for our drug candidates, which may not support further development or marketing approval; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials and marketing approval; our ability to achieve commercial success for our drug candidates, if approved; our limited operating history and our ability to obtain additional funding for operations and to complete the development and commercialization of our drug candidates; and other risks and uncertainties set forth in "Risk Factors" in our most recent Annual Report on Form 10-K and any subsequent Quarterly Reports on Form 10-Q. In addition, statements that "we believe" and similar statements reflect our beliefs and opinions on the relevant subject. These statements are based upon information available to us as of the date of this press release, and while we believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted an exhaustive inquiry into, or review of, all potentially available relevant information. These statements are inherently uncertain and you are cautioned not to rely unduly upon these statements. All information in this press release is as of the date of this press release. The information contained in any website referenced herein is not, and shall not be deemed to be, part of or incorporated into this press release.

Source: Clene Inc.

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Clene to Report HEALEY ALS Platform Trial Topline Results on Monday, October 3 - Investing News Network