Research Offers Promising Outlook for Nanomedicine – Controlled Environments Magazine

In the past six years, the National Research Programme "Opportunities and Risks of Nanomaterials" (NRP 64) intensively studied the development, use, behavior, and degradation of engineered nanomaterials, including their impact on humans and on the environment.

Twenty-three research projects on biomedicine, the environment, energy, construction materials and food demonstrated the enormous potential of engineered nanoparticles for numerous applications in industry and medicine. Thanks to these projects we now know a great deal more about the risks associated with nanomaterials and are therefore able to more accurately determine where and how they can be safely used.

"One of the specified criteria in the program was that every project had to examine both the opportunities and the risks, and in some cases this was a major challenge for the researchers," explains Peter Gehr, President of the NRP 64 Steering Committee.

One development that is nearing industrial application concerns a building material strengthened with nanocellulose that can be used to produce a strong but lightweight insulation material. Successful research was also carried out in the area of energy, where the aim was to find a way to make lithium-ion batteries safer and more efficient.

A great deal of potential is predicted for the field of nanomedicine. Nine of the 23 projects in NRP 64 focused on biomedical applications of nanoparticles. These include their use for drug delivery, for example in the fight against viruses, or as immune modulators in a vaccine against asthma. Another promising application concerns the use of nanomagnets for filtering out harmful metallic substances from the blood. One of the projects demonstrated that certain nanoparticles can penetrate the placenta barrier, which points to potential new therapy options. The potential of cartilage and bone substitute materials based on nanocellulose or nanofibres was also studied.

The examination of potential health risks was the focus of NRP 64. A number of projects examined what happens when nanoparticles are inhaled, while two focused on ingestion. One of these investigated whether the human gut is able to absorb iron more efficiently if it is administered in the form of iron nanoparticles in a food additive, while the other studied silicon nanoparticles as they occur in powdered condiments. It was ascertained that further studies will be required in order to determine the doses that can be used without risking an inflammatory reaction in the gut.

The aim of the seven projects focusing on environmental impact was to gain a better understanding of the toxicity of nanomaterials and their degradability, stability and accumulation in the environment and in biological systems. Here, the research teams monitored how engineered nanoparticles disseminate along their lifecycle, and where they end up or how they can be discarded.

One of the projects established that 95 percent of silver nanoparticles that are washed out of textiles are collected in sewage treatment plants, while the remaining particles end up in sewage sludge, which in Switzerland is incinerated. In another project a measurement device was developed to determine how aquatic microorganisms react when they come into contact with nanoparticles.

"The findings of the NRP 64 projects form the basis for a safe application of nanomaterials," says Christoph Studer from the Federal Office of Public Health. "It has become apparent that regulatory instruments such as testing guidelines will have to be adapted at both national and international level." Studer has been closely monitoring the research program in his capacity as the Swiss government's representative in NRP 64. In this context, the precautionary matrix developed by the government is an important instrument by means of which companies can systematically assess the risks associated with the use of nanomaterials in their production processes.

The importance of standardized characterization and evaluation of engineered nanomaterials was highlighted by the close cooperation among researchers in the program. "The research network that was built up in the framework of NRP 64 is functioning smoothly and needs to be further nurtured," says Professor Bernd Nowack from Empa, who headed one of the 23 projects.

The results of NRP 64 show that new key technologies such as the use of nanomaterials need to be closely monitored through basic research due to the lack of data on its long-term effects. As Gehr points out, "We now know a lot more about the risks of nanomaterials and how to keep them under control. However, we need to conduct additional research to learn what happens when humans and the environment are exposed to engineered nanoparticles over longer periods, or what happens a long time after a one-off exposure."

Source: Swiss National Science Foundation

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Healthcare Nanotechnology (Nanomedicine) Market Expected to Generate Huge Profits by 2015 2021: Persistence … – MilTech

Nanotechnology is one of the most promising technologies in 21st century. Nanotechnology is a term used when technological developments occur at 0.1 to 100 nm scale. Nano medicine is a branch of nanotechnology which involves medicine development at molecular scale for diagnosis, prevention, treatment of diseases and even regeneration of tissues and organs. Thus it helps to preserve and improve human health. Nanomedicine offers an impressive solution for various life threatening diseases such as cancer, Parkinson, Alzheimer, diabetes, orthopedic problems, diseases related to blood, lungs, neurological, and cardiovascular system.

Development of a new nenomedicine takes several years which are based on various technologies such as dendrimers, micelles, nanocrystals, fullerenes, virosome nanoparticles, nanopores, liposomes, nanorods, nanoemulsions, quantum dots, and nanorobots.

In the field of diagnosis, nanotechnology based methods are more precise, reliable and require minimum amount of biological sample which avoid considerable reduction in consumption of reagents and disposables. Apart from diagnosis, nanotechnology is more widely used in drug delivery purpose due to nanoscale particles with larger surface to volume ratio than micro and macro size particle responsible for higher drug loading. Nano size products allow to enter into body cavities for diagnosis or treatment with minimum invasiveness and increased bioavailability. This will not only improve the efficacy of treatment and diagnosis, but also reduces the side effects of drugs in case of targeted therapy.

Global nanomedicine market is majorly segmented on the basis of applications in medicines, targeted disease and geography. Applications segment includes drug delivery (carrier), drugs, biomaterials, active implant, in-vitro diagnostic, and in-vivo imaging. Global nanomedicine divided on the basis of targeted diseases or disorders in following segment: neurology, cardiovascular, oncology, anti-inflammatory, anti-infective and others. Geographically, nanomedicine market is classified into North America, Europe, Asia Pacific, Latin America, and MEA. Considering nanomedicine market by application, drug delivery contribute higher followed by in-vitro diagnostics. Global nanomedicine market was dominated by oncology segment in 2012 due to ability of nanomedicine to cross body barriers and targeted to tumors specifically however cardiovascular nanomedicine market is fastest growing segment. Geographically, North America dominated the market in 2013 and is expected to maintain its position in the near future. Asia Pacific market is anticipated to grow at faster rate due to rapid increase in geriatric population and rising awareness regarding health care. Europe is expected to grow at faster rate than North America due to extensive product pipeline portfolio and constantly improving regulatory framework.

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Major drivers for nanomedicine market include improved regulatory framework, increasing technological know-how and research funding, rising government support and continuous increase in the prevalence of chronic diseases such as obesity, diabetes, cancer, kidney disorder, and orthopedic diseases. Some other driving factors include rising number of geriatric population, awareness of nanomedicine application and presence of high unmet medical needs. Growing demand of nanomedicines from the end users is expected to drive the market in the forecast period. However, market entry of new companies is expected to bridge the gap between supply and demand of nanomedicines. Above mentioned drivers currently outweigh the risk associated with nanomedicines such as toxicity and high cost. At present, cancer is one of the major targeted areas in which nanomedicines have made contribution. Doxil, Depocyt, Abraxane, Oncospar, and Neulasta are some of the examples of pharmaceuticals formulated using nanotechnology.

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Key players in the global nanomedicine market include: Abbott Laboratories, CombiMatrix Corporation, GE Healthcare, Sigma-Tau Pharmaceuticals, Inc., Johnson & Johnson, Mallinckrodt plc, Merck & Company, Inc., Nanosphere, Inc., Pfizer, Inc., Celgene Corporation, Teva Pharmaceutical Industries Ltd., and UCB (Union chimique belge) S.A.

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Healthcare Nanotechnology (Nanomedicine) Market Expected to Generate Huge Profits by 2015 2021: Persistence ... - MilTech

MagForce AG: ‘NanoTherm School’ successfully enters its second round with Module B – PharmiWeb.com

DGAP-Media / 11.12.2019 / 09:30

MagForce AG: 'NanoTherm School' successfully enters its second round with Module B

Berlin, Germany and Nevada, USA, December 11, 2019 - With "Module B - Advanced Course 1: - stereotactic Instillation" MagForce AG (Frankfurt, Scale, Xetra: MF6, ISIN: DE000A0HGQF5), a leading medical device company in the field of nanomedicine focused on oncology, conducted the second round of its 'NanoTherm School' in November. The application training series was launched in January 2019 to provide the highest quality of treatment through ongoing support for physicians and certify surgeons in the use of the innovative NanoTherm technology. Same as the first session, "Module A - The Basics", which took place at the end of January 2019, Module B, focusing on advanced techniques, was met with great excitement from participants.

The NanoTherm School is part of MagForce's roll-out strategy focusing on a broad geographic coverage to provide greater availability while also constantly working on further optimizing its therapy system and educating medical professionals in its use to provide brain tumor patients with the best care possible. The training concept of NanoTherm School was developed in close collaboration with Prof. Dr. Walter Stummer, PD Dr. Dr. Oliver Grauer, and Dr. Michael Schwake, University Hospital Mnster, and PD Dr. Johannes Wlfer, Hufeland Klinikum GmbH Mhlhausen, drawing on their long-standing experience in the treatment of brain tumor patients with the NanoTherm therapy system.

Participants again included the team of Prof. Dr. med. habil. Jan-Peter Warnke, Senior Consultant in the Neurosurgical Clinic at the Paracelsus Clinic in Zwickau, with whom MagForce entered into a cooperation agreement in June 2019. Installation of the mobile treatment center was completed in summer. The NanoActivator is now ready for use at the clinic after receipt of final approval and and is now available for the treatment of patients with brain tumors.

Prof. Dr. med. habil. Jan-Peter Warnke, Senior Consultant in the Neurosurgical Clinic at the Paracelsus Clinic in Zwickau, added "Innovation is extremely important in medicine and has served our patients well. Obtaining the appropriate training in new technologies and techniques is a vital part of adopting these advances into our standard treatment regimens. Practical trainings such as MagForce's NanoTherm School are therefore very welcomed as they allow neurosurgeons to ease into the method while developing the necessary skills. Thanks to the excellent preparation and support of the MagForce team, as well as the opportunity to practice NanoTherm therapy in the most practical and extremely well-structured way, we are well prepared for the use of the therapy system at our clinic starting immediately. The use of new teaching methods for advanced technologies helps us to bring outstanding inventions to patients."

About NanoTherm SchoolTargeted towards medical professionals working in the fields of neuro-surgery and neuro-oncology, the NanoTherm Therapy School series aims at introducing participants to the theoretical knowledge and practical techniques required to successfully apply MagForce's NanoTherm technology for the treatment of brain tumors. In practicing their skills with human specimens, participants are able to familiarize themselves with the procedures and device usages in a stress-free environment under largely real operating conditions.

The NanoTherm School is designed in three consecutive modules allowing participants to gain knowledge and understanding of MagForce's NanoTherm technology starting from basic application techniques (nanopasting) and building to advanced techniques and new surgical application forms in the final module (Module C). The practical section of the course is complemented by lectures on directly relevant aspects of NanoTherm therapy, as well as sample preparation and surgical videos. The equipment and facilities used during the course meet the requirements of today's state-of-the-art surgical equipment.

For more information about NanoTherm School, please contact:Dipl.-Ing. Tobias Hanitsch (thanitsch@magforce.com)Marcel Pilz (mpilz@magforce.com)

About MagForce AG and MagForce USA, Inc.MagForce AG, listed in the Scale segment of the Frankfurt Stock Exchange (MF6, ISIN: DE000A0HGQF5), together with its subsidiary MagForce USA, Inc. is a leading medical device company in the field of nanomedicine focused on oncology. The Group's proprietary NanoTherm therapy system enables the targeted treatment of solid tumors through the intratumoral generation of heat via activation of superparamagnetic nanoparticles.

NanoTherm(R), NanoPlan(R), and NanoActivator(R) are components of the therapy and have received EU-wide regulatory approval as medical devices for the treatment of brain tumors. MagForce, NanoTherm, NanoPlan, and NanoActivator are trademarks of MagForce AG in selected countries.

For more information, please visit: http://www.magforce.com.Get to know our Technology: video (You Tube)Stay informed and subscribe to our mailing list

Disclaimer This release may contain forward-looking statements and information which may be identified by formulations using terms such as "expects", "aims", "anticipates", "intends", "plans", "believes", "seeks", "estimates" or "will". Such forward-looking statements are based on our current expectations and certain assumptions, which may be subject to a variety of risks and uncertainties. The results actually achieved by MagForce AG may substantially differ from these forward-looking statements. MagForce AG assumes no obligation to update these forward-looking statements or to correct them in case of developments, which differ from those, anticipated.

End of Media Release

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2017 Forecast – Asia Pacific Nanomedicine Market, Industry Size and Share to 2023 – Digital Journal

Global Market Research Report on Nanomedicine Market 2017 is a professional and in-depth complete study on the current state of the Nanomedicine worldwide.

This press release was orginally distributed by SBWire

Deerfield Beach, FL -- (SBWIRE) -- 06/19/2017 -- Latest industry research report on Nanomedicine Market. Nanomedicine is the applied branch of nanotechnology. Application of nanomedicines ranges from nonmaterial to nanoelectronic and in the near future, it could possibly expand to molecular nanotechnology. Biological, pharmaceutical and medical research organizations (CROs) are largely benefitted by the exceptional properties of nonmaterial and exploit it for various applications including diagnosis and treatment of diseases. The Asia pacific nanomedicine market is majorly driven by advancement in nanomedicine technologies, government initiatives, growing investment in research funding, better understanding of technical know-how and a high prevalence of chronic diseases.

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However, the cost of materials used in nanotechnology study along with the insufficient regulatory framework can pose a major restrain for the growth of the Asia pacific nanomedicines market. Presence of high growth opportunities in nanomedicines would provide significant benefits to emerging economies such as India and China due to the impending healthcare needs in this location.

The Asia Pacific nanomedicine market is segmented into two categories such as application and geography.

BY APPLICATION

Cardiovascular Oncology Anti-Inflammatory Anti-Infective Neurology Others

BY GEOGRAPHY

China Japan India Australia Others

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2017 Forecast - Asia Pacific Nanomedicine Market, Industry Size and Share to 2023 - Digital Journal

NanoViricides (NNVC) Abstract Accepted for Poster Presentation at ASV – StreetInsider.com

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NanoViricides, Inc., (NYSE: NNVC) a pioneer in developing anti-viral nanomedicine drugs, is pleased to announce that its late-breaking abstract submission has been accepted for a poster presentation at the 36th Annual Meeting of the American Society of Virology (ASV). The ASV Meeting will be hosted and held at the University of Wisconsin-Madison, from June 24th to 28th, 2017 (https://extensionconferencecenters.uwex.edu/asv2017/).

Dr. Brian Friedrich, Senior Virologist of the Company, will present the Company's work on the evaluation of nanoviricides drug candidates for effectiveness against the shingles virus (Varicella Zoster Virus, VZV, aka Human HerpesVirus-3 or HHV-3). He will present data on both safety and effectiveness of the nanoviricides drug candidates against VZV infection in multiple different cell lines.

NanoViricides has recently announced that two of the HerpeCide program drug candidates demonstrated complete (almost 100%) inhibition of the varicella-zoster virus (VZV, aka human herpesvirus 3 or HHV-3) at highest drug doses, whereas acyclovir at the same drug dose exhibited only about 70% inhibition of the virus. The nanoviricide drug candidates were almost five times as effective as acyclovir in these assays. No cytotoxicity was observed at any of the doses tested for the herpecide drug candidates. Details of these studies will be presented in the poster at the 2017 Annual Meeting of the ASV.

The NanoViricides poster, entitled "Novel Nanoviricides Highly Effective against Varicella Zoster Virus in Cell Culture" will be presented in Poster Session II, open for viewing from 4pm to 6pm on Monday, June 26th, 2017.

About NanoViricides: NanoViricides, Inc. (www.nanoviricides.com) is a development stage company that is creating special purpose nanomaterials for antiviral therapy. The Company's novel nanoviricide class of drug candidates are designed to specifically attack enveloped virus particles and to dismantle them. The Company is developing drugs against a number of viral diseases including H1N1 swine flu, H5N1 bird flu, seasonal Influenza, HIV, oral and genital Herpes, viral diseases of the eye including EKC and herpes keratitis, Hepatitis C, Rabies, Dengue fever, and Ebola virus, among others.

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Nanomaterials in Theranostics Market By Top Players, Latest Trends, Demand Analysis and Forecast FLA News – FLA News

Global Nanomaterials in Theranostics Market: Overview

The application of theranostics in nanomedicine is a fast emerging paradigm, which involves the use of nanoparticles or nanoscale materials for a variety of diagnostic, imaging, and therapeutic applications. Recent research efforts have been increasingly focused on designing functional nanomaterials for non-invasive imaging of diseases, including bioimaging and biosensing, advanced biomarkers, and targeted delivery of therapeutic drugs. Efforts are also underway for developing highly biocompatible nanoplatforms for various theranostic nanomedicine applications.

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Several nanomaterials in theranostics have proven promising for the treatment of chronic and fatal diseases such as cancer, AIDS, and various types of cardiovascular diseases. Adequate surface modifications are being made in a variety of polymeric and inorganic nanoparticles to enhance their conjugation with biomolecules and their interactions with target tissues. As a result, the market is witnessing the development of various classes of nanoscale particles with reduced cytotoxicity and advanced therapeutic applications, improving the quality of life for patients.

The report offers in-depth insights into the key market dynamics, current trends, and recent technological advances in nanomaterials, emerging theranostics applications, lucrative avenues, and competitive dynamics. The research study takes a closer look at several cross-disciplinary researches in drug discovery and highlights major developments in nanomaterials by leading players for expanding theranostics applications.

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Global Nanomaterials in Theranostics Market: Trends and Opportunities

The rising incidence of chronic and life-threatening diseases, coupled with the need for improving disease detection, and the demand for advanced chemotherapeutic treatments are the key factors propelling the market. The growing potential of clinically translatable nanomaterials in the areas of biological imaging and therapy is anticipated to boost the market. Continuous researches in improving the biocompatibility of a range of nanoparticles, mainly through appropriate surface modification, has fuelled the demand for nanomaterials in theranostics.

In addition, increasing applications of nanoparticles for effective target-specific drug delivery has stimulated their applications in hyperthermia-based cancer treatments, thereby bolstering the demand for nanomaterials in theranostics. Some of the most common classes of nanoparticles used in theranostic applications are gold nanoparticles, mesoporous silica nanoparticles, quantum dots, and nanocrystals.

However, lack of favorable regulatory framework, stringent approval requirements, and spiraling developmental costs are some of the key factors likely to hinder the nanomaterials in theranostics market to an extent. Nevertheless, recent partnerships and collaborations between several pharmaceutical and medical devices companies and substantial investments of biotech companies in nanoparticles are expected to unlock abundant opportunities for market players over the forecast period. Furthermore, the application of carbon-based nanoparticles for making a wide range of drug delivery systems is expected to open up lucrative avenues in the coming years.

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Global Nanomaterials in Theranostics Market: Regional Outlook

North America is one of the major markets for nanomaterials in theranostics. In the U.S., the theranostic witnesses wide applications in biosensing, bioimaging, and targeted drug delivery. Recent translational researches in the region have expanded the potential of theranostic nanomedicine for a variety of diseases, thereby boosting the nanomaterials in theranostics market.

In addition, a robust awareness among patients and clinicians in the efficacy of nanomaterials in theranostics, and aggressive efforts by manufacturers to market their products are expected to catalyze growth. Europe is another prominent market for the demand for nanomaterials in theranostics. The substantial growth of this regional market can be attributed to growing number of product approvals and vast unmet market needs.

Asia Pacific is expected to show vast opportunities for numerous manufacturers and vendors. This is attributed to increased focus on R&D activities in nanoparticles, cheap procurement of raw materials, and a rapidly rising patient population pool.

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Companies mentioned in the report

Companies vying for a sustained share in the nanomaterials in theranostics market include Abalonyx, Nanomat, Inc. Affymetrix, Aldlab Nanotech, Berkeley Advanced Biomaterials, Inc., ACS Materials, AMAG Pharmaceuticals, Inc., Applied Graphene Materials plc, A.P. Pharma, Inc., Monogram Biosciences Inc., Nanocarrier Co. Ltd., Liquidia Technologies, Inc., and Advanced Proteome.

Leading players are resorting to acquisitions and collaborations to consolidate their positions across major regions.

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The Global Nanomedicine Market is Expected to Grow at a CAGR of Around 10% During 2021-2026 – ResearchAndMarkets.com – Business Wire

DUBLIN--(BUSINESS WIRE)--The "Nanomedicine Market: Global Industry Trends, Share, Size, Growth, Opportunity and Forecast 2021-2026" report has been added to ResearchAndMarkets.com's offering.

The global nanomedicine market exhibited strong growth during 2015-2020. Looking forward, the market is expected to grow at a CAGR of around 10% during 2021-2026.

Keeping in mind the uncertainties of COVID-19, we are continuously tracking and evaluating the direct as well as the indirect influence of the pandemic on different end-use sectors. These insights are included in the report as a major market contributor.

Nanomedicine refers to specialized multi-functional drugs with programmable properties used for the treatment of diseases and repairing tissues at a molecular level.

It involves the use of nanoparticles, nanotubes and nanodevices, such as imaging agents, nanorobots, biochips and polymer therapeutics, for the diagnosis, treatment and prevention of a disorder and analyzing the underlying pathophysiology. The nanoparticles include metal and metal oxides, liposomes and inorganic particles, which are used for transporting the drugs and targeting difficult to reach areas in the body.

As a result, nanomedicine finds extensive applications for drug delivery, diagnostic imaging, vaccines, regenerative medicines and implants.

Nanomedicine Market Trends:

The increasing prevalence of chronic medical ailments across the globe is one of the key factors creating a positive outlook for the market. Nanomedicine is highly beneficial in the treatment of oncological, neurological, urological, infectious, ophthalmological, orthopedic, immunological and cardiovascular diseases.

Moreover, as the coronavirus disease (COVID-19) continues to spread across the globe, there has been a significant increase in the demand for nanomedicines to produce vaccines and nanocarrier systems with enhanced efficacies. In line with this, shifting preference for personalized medicines is also contributing to the growth of the market.

Additionally, various technological advancements in the nanoscale technologies for improved diagnostic procedures are acting as other growth-inducing factors. Pharmaceutical manufacturers are using nanorobotic systems and other novel solutions for the effective administration of nanomedicines. Other factors, including improvements in the healthcare infrastructure, along with extensive research and development (R&D) activities in the field of biotechnology, are anticipated to drive the market toward growth.

Key Market Segmentation:

The publisher provides an analysis of the key trends in each sub-segment of the global nanomedicine market, along with forecasts at the global, regional and country level from 2021-2026. Our report has categorized the market based on region, nanomolecule type, product and application.

Competitive Landscape:

The competitive landscape of the industry has also been examined along with the profiles of the key players being:

Key Questions Answered in This Report:

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Global Nanomedicine Market Top Countries Analysis and Manufacturers With Impact of COVID-19 | 2020-2026 Detail Analysis focusing on Application, Types…

Databridgemarketresearch.com Present Global Nanomedicine Market Industry Trends and Forecast to 2027 new report to its research database. The report spread No of pages: 350 No of Figures: 60 No of Tables: 220 in it. This Global Nanomedicine Market report takes into consideration diverse segments of the market analysis that todays business ask for. The Global Nanomedicine Market report provides estimations of CAGR values, market drivers and market restraints about the industry which are helpful for the businesses in deciding upon numerous strategies. The base year for calculation in the report is taken as 2017 whereas the historic year is 2016 which will tell you how the Global Nanomedicine Market is going to perform in the forecast years by informing you what the market definition, classifications, applications, and engagements are. The report helps you to be there on the right track by making you focus on the data and realities of the industry.

The research studies of this Global Nanomedicine Market report helps to evaluate several important parameters that can be mentioned as investment in a rising market, success of a new product, and expansion of market share. Market estimations along with the statistical nuances included in this market report give an insightful view of the market. The market analysis serves present as well as future aspects of the market primarily depending upon factors on which the companies contribute in the market growth, crucial trends and segmentation analysis. This Global Nanomedicine Market research report also gives widespread study about different market segments and regions.

Global nanomedicine marketis registering a healthy CAGR of 15.50% in the forecast period of 2019-2026. This rise in the market value can be attributed to increasing number of applications and wide acceptance of the product globally. There is a significant rise in the number of researches done in this field which accelerate growth of nanomedicine market globally.

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Key Market Competitors

Few of the major market competitors currently working in the global nanomedicine market are Abbott, Invitae Corporation, General Electric Company, Leadiant Biosciences, Inc., Johnson & Johnson Services, Inc., Mallinckrodt, Merck Sharp & Dohme Corp., NanoSphere Health Sciences, Inc., Pfizer Inc., CELGENE CORPORATION, Teva Pharmaceutical Industries Ltd., Gilead Sciences, Inc., Amgen Inc., Bristol-Myers Squibb Company, AbbVie Inc., Novartis AG, F. Hoffmann-La Roche Ltd., Luminex Corporation, Eli Lilly and Company, Nanobiotix, Sanofi, UCB S.A., Ablynx among others.

Competitive Landscape

Global nanomedicine market is highly fragmented and the major players have used various strategies such as new product launches, expansions, agreements, joint ventures, partnerships, acquisitions, and others to increase their footprints in this market. The report includes market shares of nanomedicine market for global, Europe, North America, Asia-Pacific, South America and Middle East & Africa.

Key Insights in the report:

Complete and distinct analysis of the market drivers and restraints

Key Market players involved in this industry

Detailed analysis of the Market Segmentation

Competitive analysis of the key players involved

Market Drivers are Restraints

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Market Segmentation:-

By Product Type

By Application

By Indication

By Modality

To comprehend Global Nanomedicine market dynamics in the world mainly, the worldwide Nanomedicine market is analyzed across major global regions.

Actual Numbers & In-Depth Analysis, Business opportunities, Market Size Estimation Available in Full Report.

Some of the Major Highlights of TOC covers:

Chapter 1: Methodology & Scope

Definition and forecast parameters

Methodology and forecast parameters

Data Sources

Chapter 2: Executive Summary

Business trends

Regional trends

Product trends

End-use trends

Chapter 3: Industry Insights

Industry segmentation

Industry landscape

Vendor matrix

Technological and innovation landscape

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Nanomedicine Market report effectively provides required features of the global market for the population and for the business looking people for mergers & acquisitions, making investments, new vendors or concerned in searching for the appreciated global market research facilities. It offers sample on the size, offer, and development rate of the market. The Nanomedicine report provides the complete structure and fundamental overview of the industry market.

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Global Nanomedicine Market Top Countries Analysis and Manufacturers With Impact of COVID-19 | 2020-2026 Detail Analysis focusing on Application, Types...

Protein-avoidant ionic liquid (PAIL)coated nanoparticles to increase bloodstream circulation and drive biodistribution – Science Advances

Abstract

The rapid clearance of intravenously administered nanoparticles (NPs) from the bloodstream is a major unsolved problem in nanomedicine. Here, we describe the first use of biocompatible protein-avoidant ionic liquids (PAILs) as NP surface modifiers to reduce opsonization. An ionic liquid choline hexenoate, selected for its aversion to serum proteins, was used to stably coat the surface of poly(lactic-co-glycolic acid) (PLGA) NPs. Compared with bare PLGA and poly(ethylene glycol)coated PLGA particles, the PAIL-PLGA NPs showed resistance to protein adsorption in vitro and greater retention in blood of mice at 24 hours. Choline hexenoate redirected biodistribution of NPs, with preferential accumulation in the lungs with 50% of the administered dose accumulating in the lungs and <5% in the liver. Lung accumulation was attributed to spontaneous attachment of the PAIL-coated NPs on red blood cells in vivo. Overall, ionic liquids are a promising class of materials for NP modification for biomedical applications.

Nanomedicine offers an alluring promise for drug deliverythe capacity to administer therapeutics to specific parts of the body while minimizing off-target effects seen with systemic administration of drugs, particularly chemotherapeutics (1). However, despite decades of excellent work in the field, only a handful of nanoparticles (NPs) have made it through clinical trials (2). One large barrier to translation of nanomedicines is the removal of the NPs from the bloodstream (3). Once injected intravenously, the NPs encounter a diversity of serum proteins that adhere to the surface of the particle to form a protein corona (4), alerting the immune system to a foreign invader, which then swiftly removes the vast majority of the injected NPs to the filtering organs, primarily the liver (5), for clearance from the body.

The current gold standard for reducing NP clearance is the use of poly(ethylene) glycol (PEG) coatings, which reduces clearance by increasing the hydrophilicity of the surface of the particle, thwarting the attachment of the circulating proteins (6). However, the widespread usage of PEG in many consumer products, and the simplicity of its chemical structure, has led to an estimated 25% of the general population developing anti-PEG antibodies (7), mainly anti-PEG immunoglobulin M (8). A recent clinical review of the immunogenicity of PEG included a report of the use of PEGylated uricase for the treatment of critical gout. Of 169 human patients, 89% developed high anti-pegloticase antibody response (9), which resulted in rapid clearance and injection-site reactions after the first injection, overwhelming any beneficial effect of the administered therapeutic. Therefore, strategies to avoid NP clearance that require alternatives to PEG are needed in the toolbox of nanomedicine.

Ionic liquids (ILs), which consist of asymmetric, bulky cations and anions that have melting points below 100C (10), have been used across a broad range of applications, including synthesis (11), catalysis (12), and battery applications (13). They have a number of appealing properties, one of which is inherent tunability, where a small change in the chemical structure of one of the components results in a measurable shift in observed bulk properties (14). When synthesized from biocompatible materials, ILs have shown great promise in biomedical applications (15), including stabilizing proteins (16), drug delivery through the skin (1719), and oral drug delivery (20), where the components of ILs can be selected to optimize physiologically relevant properties, such as membrane interaction (21). ILs have been used to coat NPs in nonbiological settings, such as catalysis (22) and sensing platforms (23), and some preliminary studies have evidenced their suitability in improving the biocompatibility of existing carriers (24). However, the versatility and tunability of ILs have not yet been exploited in the context of coating NPs to reduce opsonization in intravenous drug delivery. We hypothesized that ILs can be designed to coat NPs to reduce protein adsorption and opsonization. This hypothesis was inspired by the success of zwitterionic surfactants in reducing surface protein adsorption (25, 26). Here, we developed and synthesized a library of biocompatible ILs and screened for those that do not solvate proteins wellso-called protein-avoidant ionic liquids (PAILs). Upon incubation with NPs, PAILs spontaneously coat the surface of NPs with PAILs and form a stable coating. PAIL coating delays protein adsorption on the NP surface and reduces clearance of intravenously injected NPs in vivo.

Poly(lactic-co-glycolic acid) (PLGA) was chemically conjugated to 1,1-dioctadecyl-3,3,3,3-tetramethylindodicarbocyanine, 4-chlorobenzenesulfonate salt solid (DiD) dye, and PLGA NPs were synthesized by surfactant-free nanoprecipitation to generate bare control NPs (see Methods). PEG was chemically conjugated to PLGA NPs to generate PEGylated-PLGA NPs. A library of choline-based ILs was synthesized to coat NPs (table S1). Choline was used as a cation because of its biocompatibility and prior history of use in humans. Choline is a dietary supplement and closely related to a neurotransmitter acetyl choline (27). Various anions were used to synthesize ILs. A range of carboxylic acidbased anions were tested, with carbon chain lengths of four to eight and with varying unsaturation, ring structures, and number of oxygen atoms. Ion ratios of 1:1 to 1:6 (cation:anion) were also tested. ILs were allowed to coat NPs through a 3-hour incubation with stirring, followed by filtration. The synthesized NPs were then characterized with nuclear magnetic resonance (NMR) spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM; for the choline hexenoate 1:2 particles). The ability of ILs to coat NPs was confirmed by NMR (presence of IL components), DLS (changes in NP sizes), and TEM for the lead IL, choline hexenoate.

The capping ability of ILs varied greatly with their composition. ILs were considered to have successfully capped the PLGA NP if, after the modification and filtration process, monodispersed [polydispersity index (PDI), <0.3] peaks appeared by DLS with hydrodynamic diameters <300 nm. ILs with ring structures, presence of oxygen atoms beyond the carboxylic acid functional group, and unbranched carbon chains shorter than six were not able to stably cap the NPs. Ion ratio also affected NP capping. Among the ILs with eight carbon anions, 1:2 octanoic acid created much smaller particles than its 1:1 counterpart. In the case of geranic acid, all ion ratios produced stably capped particles except 1:6. Figure 1 shows the full characterization of particles coated with choline hexenoate 1:2.

(A) 1H NMR spectrum of PLGA NPs surface coated with choline hexenoate (1:2). (B) DLS reported hydrodynamic diameter of NPs (log10 transformation on the x axis) when bare (black), coated with PEG (blue), and coated with IL (red) with mean diameters above each curve. (C) DLS reported zeta potential of NPs when bare (black), coated with PEG (blue), and coated with IL (red). (D) TEM of bare PLGA particles. (E) TEM of PEG-capped particles. (F) TEM of IL-coated particles. Scale bars, 200 nm.

Presence of choline hexenoate on NPs was confirmed by proton NMR (Fig. 1A). From integration of the peaks corresponding to the choline and hexenoate, each component appears in molar equivalencyi.e., 1:1, despite adding a 1:2 ratio to the synthesis procedure. Addition of choline hexenoate slightly increased the diameter of the NPs as measured by DLS (Fig. 1B). Bare PLGA NPs (black) had an average diameter of 64.60 9.41 nm (PDI = 0.135). PEGylation increased the NP diameter to 123.1 14.8 nm (PDI = 0.2) (blue). IL-NPs (red) exhibited the largest diameter of 170.0 19.1 nm (PDI = 0.16) (Fig. 1C). Corresponding changes were also observed in the surface charge of the NPs. Bare NPs (black) had the average zeta potential of 11.0 4.03 mV. PEGylated NPs (blue) had a zeta potential of 31.3 5.86 mV. IL-NPs (red) exhibited the most negative surface charge of 40.5 2.12 mV. TEM indicated substantial changes in the morphologies of NPs (Fig. 1D). Bare PLGA NPs exhibited uniform composition, and size of NPs generally matched those determined from DLS. PEGylated NPs exhibited a high-contrast core surrounded by a ring of lower contrast around the PLGA core (Fig. 1E). IL-NPs exhibited a peculiar structure where the high-contrast core was surrounded by a much larger core of lighter contrast than the polymeric core (Fig. 1E), evidencing the successful surface modification of the PLGA NPs. Figure S4 shows the population size distribution (BD) by TEM. The IL-NPs retained this size and negative surface charge with an acceptable PDI for >3 weeks (figs. S1 to S3), only falling apart at 3.5 weeks, at which point the ester linkages in the PLGA likely begin to undergo hydrolysis (28), as seen by the PDI of the bare particles approaching 1 at the 3.5-week mark. This is consistent with earlier reports of 50:50 PLGA particles undergoing in vitro degradation after 21 to 26 days (29).

The serum stability and compatibility of IL-NPs were tested by incubating them with whole-mouse serum. IL-NPs maintained their stability in serum for various periods of time depending on the IL composition (table S2). IL-NPs resisted size increase for a composition-dependent time period, followed by a monotonic size increase. The duration of no size growth was considered as an indicator of the ability of IL-NPs to resist protein corona formation.

The identity of the anion played a significant role in protecting the NP from protein adsorption. Anions with carbon chains six to eight carbons in length emerged as the best at resisting protein adsorption. The role of the double bond emerged as a critical factorthe addition of a double bond to hexanoate to create hexenoate improved the resistance to serum by a factor of 22. In the case of the serum test, the role of the ion ratio is anion dependent. For the hexenoate, the 1:2 ratio outperforms the 1:1 IL by sixfold, but for geranic acid, the 1:1 ratio outperforms the others by twofold.

The most successful candidate of the library of ILs tested was choline hexenoate (1:2). Therefore, it underwent further testing and is hereafter referred to as PAIL.

Stability of NPs against aggregation was tested in undiluted mouse serum in a timed DLS test. The diameter of bare PLGA particles, shown as black diamonds, increased within minutes to 200% of their original size (Fig. 2A). This is consistent with numerous reports on the formation of protein coronae on polymeric particles (6, 7, 30). The PEGylated particles (blue circles) fared better than the bare NPs, only growing 60% larger than their original measured size in buffer over 30 min. The PAIL-coated particles (red squares) exhibited no appreciable size change even after 60 min in neat serum, only changing size after 90 min. The surface charge of the particles was measured at the conclusion of the serum test (Fig. 2B). The surface of the bare particles is very close to neutral, while both the PEG and PAIL show zeta potentials of 15 mV. SDSpolyacrylamide gel electrophoresis (SDS-PAGE) was performed to qualitatively investigate the degree of protein adsorption after 2 and 20 min in neat serum, evidencing that the PAIL-coated particles show a significantly smaller degree of protein adsorption. In vitro hemolysis of the particles was assessed with isolated mouse red blood cells (RBCs) (Fig. 2C). All particles showed minimal (<10%) hemolysis [no significant difference by analysis of variance (ANOVA) analysis, P = 0.96], indicating their suitability for further intravenous testing.

(A) Relative percentage increase in NP hydrodynamic diameter over time in serum from original size by DLS (n = 4), with bare NPs shown in black, PEGylated NPs in blue, and PAIL-NPs in red. (B) Zeta potential (n = 3) measured at the final time point, showing that PEG and PAIL-capped particles have a similar surface charge. (C) SDS-PAGE from a 12% gel with tris-Gly running buffer. Left to right: Ladder, PLGA 2 min, PLGA 20 min, PEG 2 min, PEG, 20 min, IL 2 min, IL 20 min. (D) Hemolysis (n = 4) of mouse RBCs in vitro show ILs do not induce significantly more hemolysis than controls (one-way ANOVA, P = 0.9586, F = 0.0425). All experiments were performed ex vivo with at least duplicate internal readings/sample/trial. All error bars are reported in SEM.

PAIL-NPs were administered intravenously via tail vein into healthy BALB/c mice (Fig. 3A). Bare NPs exhibited rapid clearance with only 20% NPs remaining in circulation after 20 min (black diamonds). PEGylated NPs exhibited improved circulation over bare NPs with 14.2 2.7% NPs remaining in circulation after 24 hours. PAIL-NPs exhibited the highest circulation with 23.6 0.86% NPs remaining in circulation after 24 hours (P = 0.02 between PEG and PAIL-NPs). At the conclusion of the 24 hours, the major organs were excised, examined by IVIS (in vivo imaging system) imaging (Fig. 3C), and quantified by fluorescence spectroscopy (Fig. 3B).

(A) Mouse 24-hour in vivo bloodstream circulation profile. Percentage of tail veininjected dose measured at each time point, with bare particles in black, PEG coated in blue, and IL coated in red. n = 6. IL-coated particles outperform PEG particles and are significantly more highly detected than uncoated PLGA NPs at 24 hours (one-way ANOVA; 24 hours: P = 0.000031, F = 22.47, followed by t test: paired two-tailed sample for means: P = 0.00202). (B) In vivo organ biodistribution profile of NPs at 24 hours by major blood-filtering organs. Represented as percentage of tail veininjected dose. Inset shows the direct [lung:liver] ratio of the IL, PEG, and bare NPs. n = 6, ***P < 0.001,**P < 0.01, and *P < 0.05 (one-way ANOVA verified by t test: paired two-tailed sample for means). (C) Twenty-four hours post IV injection activated in vivo mouse IL-6 concentrations in the plasma (pg/ml). (n = 4), t test: paired two-tailed sample for means: **P < 0.005, ***P < 0.001, and ****P < 0.0001. (D) Representative IVIS images of whole major blood-filtering organs at 24 hours after injection. All error bars are reported as standard error of the mean.

In the case of the bare particles (Fig. 3B, black), 50% of the administered dose accumulated in the liver. Most of the PEGylated particles (blue) were also found in the liver 24 hours after injection. The PAIL-NPs, however, were predominately located in the lungs, with 50% of the administered dose accumulating in the lungs. High lung/liver ratio was observed for PAIL-NPs (~12), which was >200-fold greater than that for bare NPs or PEGylated NPs. IVIS images confirmed high lung accumulation of PAIL-NPs (Fig. 3D). The IVIS images of the major organs of all six mice across the treatment groups can be found in figs. S5 to S7. Note that the fluorescence that appears in the brain across all treatment groups is likely to be autofluorescence and does not reflect any accumulation of NPs in the brain.

Systemic toxicity of IL-NPs was assessed by measuring interleukin-6 (IL-6) in the blood to investigate the possibility of inflammation induced by NPs 24 hours after injection. Both the bare and PEGylated particles show significant levels of IL-6 at a concentration of ca. 100 pg/ml, while the PAIL-NPs show >2-fold lower values at <40 pg/ml (Fig. 3C).

To investigate the reason for high lung accumulation of PAIL-NPs, RBCs from mice were evaluated by both SEM and fluorescence-activated cell sorting (FACS). Figure 4 (A and B) shows the RBCs after injecting bare (A) and PEG-PLGA particles (B). RBCs harvested from mice injected with PAIL-NPs indicated presence of NPs on the RBC surface (Fig. 4C). These NPs were not seen in mice injected with bare NPs (Fig. 4A). RBCs were also incubated with PAIL-NPs in vitro and exhibited attachment (Fig. 4D). The imaged RBCs and plasma were also analyzed using FACS. Figure 4 (E and F) shows the results for RBC and plasma after injection of bare PLGA particles, where no fluorescence is observed when gated for the DiD dye in the RBC fraction, but a large amount of fluorescence appears in the plasma. PAIL-NPs, however, exhibited high attachment to RBCs (Fig. 4G) and minimal presence in the plasma (Fig. 4H).

(A to D) SEM of RBCs withdrawn from mice after being treated with (A) bare PLGA NPs, (B) PEG-PLGA NPs, and (C) PAIL-NPs. (D) PAIL-NPs treated in vitro. Scale bars, 400 nm. Black arrows indicate NPs. (E and F) FACS 24 hours after injection of (E) bare NPs RBCs, (F) bare NPs in plasma, (G) PAIL-NPs in RBCs, and (H) PAIL-NPs in plasma.

The clearance of NPs from the bloodstream after intravenous injection remains a pressing issue even as new, promising, nanomedicines are reported near daily. Agents other than PEG are needed to overcome the immune challenges generated by its overuse. PLGA NPs were successfully coated with choline hexenoate to generate PAIL-NPs (Fig. 1). The PAIL-NPs exhibit a larger hydrodynamic radius and a more negative surface charge compared with the bare and PEGylated particles, indicating successful modification. The PLGA core has a slight negative surface charge, meaning that the layer closest to the core consists of the cation. The final, negative surface charge of the particle indicates that the terminal layer consists of anions.

The arrangement of ILs at a charged surface is a well-known phenomenon in contexts such as electrochemistry, where the ionic components arrange spontaneously in an alternating fashion at a charged surface, such as an electrode, to form an electrical double layer. Atkin and Warr (31) used atomic force microscopy to analyze ILs at mica, silica, and graphite surfaces, finding that the cations and anions arranged in alternating layers and that each layer was approximately 1 nm thick. This modification process can be likened to a layer-by-layer approach (32), except in this case, the process happens in one pot and is controlled by electrostatics rather than sequential addition of materials with alternating charges.

Zwitterionic polymers have been previously shown to exhibit stealth capabilities (26, 33). Specifically, quaternary ammoniumcarboxylic acidterminated zwitterions have been used to successfully resist fouling in 50% fetal bovine serum (25). ILs offer a modular material that offers outstanding tunability of parameters. They, thus, offer an excellent addition to the available set of tools for controlling NP surface properties.

The NMR data show, through quantitative peak integration using tetramethylsilane, that despite adding a 1:2 ratio of cation:anion, the IL modifies the NP at an equal molar ratio of 1:1. When a 1:1 ratio is added in the case of choline hexenoate, the resulting coating is less able to resist the serum proteins, suggesting that the excess of anion confers a benefit when self-assembling around the PLGA core in the case of this anion.

The results of the in vitro serum test indicate that the PAIL-NPs outperform the conventional PEGylated particles. The primary mechanism of PEGs ability to resist serum proteins has been as attributed to its hydrophilicity. The data reported here suggest that the way in which PAILs protect the NP is more complex. Compared with the lead candidate anion (hexenoate), hexanoate has the same structure but lacks the double bond in the 2 position. This simple change in anion composition resulted in significantly reduced ability of the capped NPs to resist serum adsorption. The removal of this double bond has a marked effect on its ability to protect the NP from serum proteins, with the choline hexanoate particles increasing in size by 178.4% within 10 min. Comparatively, the lead candidate choline hexenoate 1:2 is able to resist any size change in pure serum up to 90 min. We hypothesize that the protein avoidance comes from poor solvation of the proteins, such that the proteins actively avoid interacting with the IL layering around the NP. Anions that contain oxygen atoms (other than the carboxylic acid functional group) performed significantly more poorly in capping ILs than those without additional oxygen atoms. This may be due to specific interactions occurring between the electronegative oxygen atoms and pockets of the proteins. Solvation of cytochrome c has previously been reported for choline dihydrogen phosphate by Forsyth et al. (34), where they hypothesize that its ability to act as both a hydrogen bond acceptor and donor enables its capacity to stabilize the protein, including its secondary structures.

At the conclusion of the serum test, the surface charge of the particles was measured. The bare particles showed neutralized surfaces, while both the PEGylated and PAIL-NPs retained negative zeta potentials of ca. 15 mV. The serum-exposed particles were then examined by SDS-PAGE after 2 and 20 min of exposure. Across all molecular weights, the PAIL-NPs show very faint or nonexistent bands, indicating that the PAIL-NPs have successfully lowered protein adsorption relative to the bare and PEG controls. This experiment was carried out by mixing the NPs with pure serum, which exposes the NPs to a very high concentration of protein, resulting in significant adsorption even in the case of the PEGylated particles.

The low levels of hemolysis of mouse RBCs in vitro (<10%) suggest that the PAIL-NPs do not induce cell lysis, which is an important factor in developing new agents delivered intravenously. More broadly, consideration of toxicity is critical when selecting ILs to screen, and as such, the components chosen to make the ILs were selected to ensure that they have high biocompatibility. The lead anion, trans-2-hexenoic acid, is on the Generally Regarded as Safe list and is used as a food additive to alter flavor and fragrance (35).

The in vivo testing of the NPs in healthy BALB/c mice showed that, once again, the PAIL-NPs outperformed both the PEGylated and bare controls, showing the greatest retention in the bloodstream of the mice at 24 hours. The use of PAIL-NPs instead of the control NPs resulted in a >2-fold reduction in inflammatory cytokine IL-6, suggesting the particles were far less immunostimulatory than the controls. In addition, the use of the PAIL coating substantially altered the BD of the particles, leading to a significant reduction in hepatic accumulation at 24 hours. Instead, 50% of the administered dose appeared in the lung tissue, with a lung:liver ratio of ca. 12 for the PAIL-NPs. Taking a closer look at RBCs removed from the mice 24 hours after injection using electron microscopy reveals the mechanism of this altered BD. RBCs examined from PAIL-NPtreated mice show both adhered NPs and shear marks on the surface of the RBC. No adherence is seen in RBCs removed from mice in the other treatment groups. When PAIL-NPs are exposed to RBCs in vitro, 50% of the NPs added appear attached to the surface of the RBCs. Our hypothesis for this phenomenon is that given the poor solvation of the serum proteins, the RBCs are the most abundant surface that the NP comes into contact with after injection. The precise mechanism for the interaction between the RBCs and the PAIL-NPs is yet to be uncovered, but a working hypothesis is that the terminal anionic layer of the PAIL-NPs interacts electrostatically with the abundant cationic lipids (namely, phosphatidylcholine and sphingomyelin, which are very structurally similar to the cation of the IL) in the outermost layer of RBCs. This kind of electrostatic interaction has been reported before in the case of negatively charged silica NPs, where the interaction of the NPs with RBC surfaces resulted in hemolysis (36). However, the alternating charge composition of the IL-NPs do not result in a high degree of hemolysis, perhaps because the cationic layer of IL is able to shield the terminal anionic layer, which prevents the IL-coated NP from entering the membrane to the point of rupture.

The data presented in Fig. 4 strongly suggest that PAIL-NPs attach to the surfaces of RBCs in the bloodstream after injection and are systemically circulated until they encounter the dense capillary beds, which shear the particles off into the endothelium of the surrounding blood vessels (37). When injected into the tail vein, the lung tissue is the first dense capillary bed encountered by circulating RBCs. This hitchhiking phenomenon has been reported previously (37), with two substantial differences. First, PAIL-NPs spontaneously adhere to the RBCs in the bloodstream, while previous methods required an ex vivo treatment to observe attachment. Second, the PAIL-NPs remain in the lung tissue at 50% of the injected dose at 24 hours and are not cleared by the RES (reticuloendothelial system), while previous hitchhiked NPs only showed preferential accumulation after 6 hours of administration.

The results presented here show the potential of ILs in enhancing the capabilities of NPs for drug delivery, especially given their large compositional diversity (11) and the high degree of tunability. Many exciting questions and possibilities need future attention, including understanding the specific interactions between the ILs and the proteins in the serum and the mechanisms of their interactions with the RBC surface. With further research focused on mechanisms and safety, IL-coated NPs open new opportunities in drug delivery.

Here, we report the first use of biocompatible ionic solvents as NP surface modifiers for reducing opsonization. Choline hexenoate emerged as the leading PAIL, stably attaching to the surface of PLGA particles. The PAIL-NPs showed excellent resistance to protein adsorption in vitro and, when administered in vivo, provided greater retention in the bloodstream compared with PEGylated and bare NPs. PAIL also substantially altered the BD of the NPs, with 50% of the administered dose accumulating in the lungs. Electron microscopy of RBCs at the conclusion of the experiment showed that this altered BD was a result of the PAIL-NPs spontaneously adhering to the RBCs in the bloodstream. Overall, we demonstrate the potential of the use of ILs as materials in NP drug delivery.

Choline bicarbonate, trans-2-hexenoic acid, acetonitrile [high-performance liquid chromatography (HPLC) grade, 99.8% purity], phosphate-buffered saline (PBS), D2O, Resomer RG 504 H, poly(d,l-lactide-co-glycolide) 50:50 (PLGA) with molecular weight (MW) 38,000 to 54,000 kDa and that was carboxylic acid terminated, PEG (MW 8000), and tetramethylsilane were obtained from Sigma-Aldrich (St. Louis, MO). DiD was obtained from Thermo Fisher Scientific.

Synthesis of ILs. Various carboxylic acids dissolved in ultrapure water were reacted with choline bicarbonate in a specified molar ratio (cation:carboxylic acid) at 40C for 12 hours. A rotary evaporator was then used to dry the resulting ILs at 20 mbar at 60C for 2 hours. The residual water was removed under a pressure of (760 mmHg) at 60C for 48 hours. 1H NMR characterization was performed and was found to be consistent with the previously published spectra (19).

NP core synthesis. PLGA was dissolved into HPLC-grade acetonitrile (ACN) at 1 mg/ml and vortexed for 5 min to ensure homogeneity. The far-red fluorescent dye DiD was then added into the PLGA/ACN organic phase solution at a concentration of ~1% (maximum capacity, 3%) by mass of PLGA. The final organic-phase solution was observed to turn a bright light-to-medium turquoise blue color after vortexing for another 5 min to suspend the DiD in the PLGA solution.

To synthesize uncapped PLGA NPs containing fluorescent DiD dye, 2 ml of the previously described organic-phase [(1 mg PLGA/1 ml ACN) with 1% by mass PLGA fluorescent dye] formulation was added slowly dropwise to the aqueous phase (3 ml of Milli-Q water or 3 ml of D2O for 1H NMR analysis) and allowed to stir in open air for 3 hours in the dark (38). After 3 hours of mixing in open air to achieve solvent evaporation, the uncapped NP solution was then removed from the magnetic stirring apparatus and stored in the dark at 4C in a 1.5-ml centrifuge tube.

Synthesis of PEG-capped PLGA NPs (PEG-PLGA-DiD NP). To synthesize PEG-capped PLGA NPs containing DiD dye, PEG was pre-added to the aqueous phase (3 ml of Milli-Q or D2O water) at a [2.5:1] PEG:PLGA mass/mass ratio between the PEG in the aqueous phase and PLGA in the added organic phase. This aqueous solution was left to mix for 30 min in open air in the dark via a magnetic stir bar in the round-bottom flask. Two milliliters of the previously described organic-phase PLGA formulation was then added slowly dropwise to the aqueous phase and allowed to stir in open air for 3 hours.

Synthesis of IL-capped PLGA NPs (PAIL-PLGA DiD NP). After the uncapped NPs were synthesized, they were stored in the dark in 1.5-ml centrifuge tubes at 4C for about 1 hour to stabilize before neat-synthesized IL was added all at once via pipette directly to the center vortex of a solution of uncapped NPs at a concentration of 10 mg neat IL/mg PLGA under magnetic stirring conditions in open air and allowed to mix for another 3 hours to allow for the PLGA surface self-assembly capping process.

NP filtration and storage. Both PEGylated and PAIL-modified NP solutions were then centrifuge filtered in Amicon Ultra-4 centrifugal filter units, 10K MWCO (Millipore, 4 ml) at 3000 rpm for 50 min to eliminate unbound IL or PEG (8 kDa) in the NP solution. The resultant filtered NPs were then washed in MilliQ, 1 PBS (pH 7.4), or D2O water and filtered at the same parameters. The final filtered NPs were then brought up to 1 ml in D2O or MQ-H2O for in vitro characterization. NPs were brought up to 1 ml with 1 PBS (pH 7.4) for in vitro physiological/biological work or 0.9% isotonic physiological saline for immediate use in vivo work and stored in the dark at 4C in 1.5-ml centrifuge tubes.

NMR spectroscopy. Spectra were recorded on an A600a Agilent DD2 600 MHz NMR spectrometer. Each sample contained 1000 l (2 mg) of NPs in D2O. Neat tetramethylsilane (TMS) was used additionally for quantitative NMR as an internal reference standard at a known amount of 4.5 mg (density = 0.648 g/ml at 25C, MW 88.22 g/mol).

DLS was performed on a Zetasizer ZEN3600 (Malvern, UK) in a disposable polystyrene cuvette (hydrodynamic radii) or DTS1070 (zeta potential) cell at 25C. Each sample (100 l) was diluted up to 1000 l (1:10) in H2O.

Quantification of fluorescence was achieved with a Spectramax i3 plate reader (Molecular Devices, San Jose, USA) using Corning Costar 96-well assay black and clear bottom plates (#3603) at excitation/emission wavelengths of 644 and 670 nm. A calibration curve was obtained by serial dilution with acetonitrile over a concentration range of 0.01 109 to 9.54 109 mg/ml. Each well contained 200 l. The experimental samples were measured in quadruplicate.TEM was performed via a Hitachi 7800 TEM at 80.0 kV using copper TEM grids (Electron Microscopy Sciences, carbon film 300 mesh copper). The samples were prepared by drop-casting a diluted NP solution (2 l/1 ml of MQ-H2O), negative staining with 2% uranyl acetate, and washing with MQ-H2O, and stored in a dry and dark TEM grid box for 24 hours.

NP size kinetics in neat mouse serum (by DLS). Disposable polystyrene cuvettes were used in a Malvern Zetasizer at 25C to monitor the size changes of the NPs in mouse serum. Control spectra were recorded both for the NPs at 1:10 dilution in MQ-H2O and neat mouse serum. One hundred microliters of surface-unmodified, PEG-coated, and IL-coated PLGA NP samples was separately diluted up to 1000 l (1:10) in neat whole commercial mouse serum (Invitrogen, #10410). Each samples size in serum was measured from 2 to 100 min and actively examined for any size shifts every ~4 to 6 min from the original control (MQ-H2O) peak population. This continued until the NP population peak in serum was observed to begin shifting toward 200+ nm from the original MQ-H2O NP reference peak, indicating the starting point of protein adsorption and protein corona formation.

NP zeta potential kinetics in neat mouse serum. NPs were diluted (100:1000 l) in whole normal mouse serum and incubated at 25C up until the terminal size point, with occasional gentle pipette aspiration and ejection to simulate in vivo flow conditions. To minimize damage to the gold electrode plates in the zeta potential cell by whole neat serum, centrifuge filtration was performed twice and the sample was reconstituted in 2 ml of MQ-H2O each time, as a modified protocol by Partikel et al. (30), at 1500 rpm for 15 min each (30 min total per sample) to gently flush through unbound serum proteins and preserve PLGA NP integrity. Each samples final filtrate was then brought up to 1 ml in MQ-H2O, and zeta potential values were respectively measured in cleaned and prepared zeta potential DTS1070 cells.

SDS-PAGE following incubation in neat mouse serum. NPs were mixed into whole normal mouse serum (200 l NPs:800 l neat serum) and incubated at 25C for two time points2 and 20 min. After treating with neat serum, each sample was centrifuged thrice for 15 min at 3000 rpm. After each centrifugation, 800 l of the upper nonadsorbed serum phase was carefully removed and replaced with an equivalent volume of 1 PBS (pH 7.4), thoroughly mixed by pipetting, and allowed to rest for 5 min. A final, fourth, centrifugation was performed for 10 min for each sample, after which the final NP sample was carefully isolated and transferred to a fresh tube. Laemmli buffer was added to each sample at a 1:1 ratio to each sample and subjected to a 100C degradation for 5 min. SDS-PAGE (12%, tris-Gly-SDS running buffer, 20-l loading, Bio-Rad) was then performed for 30 min at 200 V. The gel was washed three times for 5 min each in 200 ml of MQ-H2O. Water was removed, and the gel was covered with ready-to-use Coomassie stain and shaken slowly for an hour. The gel was briefly washed with MQ-H2O again and then destained with 50% HPLC methanol solution and 10% glacial acetic acid solution until the background was removed and the ladder/bands were clearly visible. Last, the gel was washed with MQ-H2O again to remove the excess destaining solution and then imaged using an iPhone camera.Kinetic hemolysis assays were performed using a modified protocol adapted from Evans et al. (39), in which 250 l of whole blood was exsanguinated from a wild-type adult BALB/c mouse 3 months of age immediately postmortem via CO2 induction and delivered into a K2-EDTAcoated vacutainer tube to prevent coagulation. Whole blood was then centrifuged at 1000g for 10 min, and then plasma was discarded to isolate the RBC pellet. The RBC pellet was then restored to 250 l with 1 PBS (pH 7.4) and centrifuged at 500g for 5 min. This wash was repeated twice more. Four hundred ninety microliters of 1 PBS (pH 7.4) was then pipetted into each of 4 ml 1.5 ml conical tubes. Washed isolated erythrocytes (10 l) were then added into each tube to produce a 1:50 dilution. These tubes constituted the stocks of diluted RBCs.

In a 96-well clear plate, each well received 20 l of control or NP solution + 180 l (1:10) of diluted RBC stock. The positive internal control was denoted as 20 l of 20% Triton X-100 into 180 l of diluted erythrocytes. The negative internal control was denoted as 1 PBS (pH 7.4) at the same dilution. The 96-well plate with samples was incubated at 37C for 1 hour and then centrifuged at 500g for 10 min. After centrifugation, 100 l of supernatant was collected and transferred from each treatment well into a new clear, flat-bottomed 96-well plate, which was then measured for peak absorbance at an experimentally determined 405 nm on a Spectramax i3 plate reader as a kinetic measurement over 2 hours at 25C. For analysis of data, the absorbance readings from 1 PBS (pH 7.4) negative internal control (0%) were used to subtract background measurement for all samples. From there, all quadruplicate measurements were normalized as a percentage of hemolysis to the Triton X-100 positive internal control (100%).

Animals. Female BALB/c mice (12 weeks of age) were purchased from Charles River Laboratories (MA, USA). All experiments were performed according to the approved protocols by the Institutional Animal Care and Use Committee of the Faculty of Arts and Sciences, Harvard University, Cambridge.

Healthy 3-month-old adult female BALB/c mice were used to evaluate pharmacokinetics (PK) and BD of the NPs. The study used the following four groups for BD and PK studies in healthy BALB/c mice: (i) ~70-nm spherical PLGA DiD particles (negative control), (ii) ~120-nm spherical PEG-PLGA DiD particles (positive control), (iii) ~180-nm spherical CAHA (Choline 2-hexenoate) 1:2 PLGA DiD particles, and (iv) 0.9% saline internal control injection. One hundred microliters of PLGA, PEG-PLGA, and CAHA 1:2-PLGA NPs in 0.9% physiological saline (final concentration, ~1 1012 NPs) was administered intravenously by tail vein injection in parallel for BD and PK purposes (n = 6). To perform pharmacokinetic studies, ~40 l of blood per mouse was taken from the submandibular vein without injection (0 min) and immediately after (within 2 min) injection, as well as at 1, 6, and 24 hours. Extracted aliquots of blood during the study were analyzed on a fluorescence plate reader to quantify the number of NPs in circulation as a percentage of the administered dose. To do this, blood extracted was directly delivered into K2-EDTAcoated tubes and immediately stored in the dark at 4C to efficiently preserve and quantify NP fluorescence.

After acquiring blood at the 24-hour time point, fluorescence for all samples time points was measured as described above. To quantify the relative percentage of NPs remaining in circulation after injection at each blood sample time point, the background fluorescence [relative fluorescence unit (RFU)] of untreated blood (time 0) was first subtracted from all blood samples at 2 min, 1 hour, 6 hours, and 24 hours. After background subtraction, the raw fluorescence (RFU) at 1, 6, and 24 hours were then compared to that of 2 min (100% fluorescence of administered dose) to obtain the percentage of NPs remaining in circulation after injection over time.

At the 24-hour terminal blood sampling time point, each mouse was exsanguinated under isoflurane anesthesia to collect final aliquots of blood for postmortem characterization [FACS, enzyme-linked immunosorbent assay (ELISA), and SEM] and then immediately euthanized by CO2 to collect main blood-filtering organs (heart, kidneys, lung, liver, spleen, and brain) for the BD study. Following modified and combined protocols originally from Oliveira et al. (40) and McGowan and Bidwell (41), a BD study was performed to measure the accumulation of the NPs in the organs. Immediately after extraction after euthanasia, organs were preserved within 50-l Falcon tubes in 4% methanol-free paraformaldehyde for 2 hours and then transferred to and washed several times in 1 PBS (pH 7.4). Immediately after washing in PBS, samples were then transferred to a petri dish, and IVIS small animal imaging was performed at 644 and 670 nm to visualize epifluorescence from the organs in units of radiant efficiency [(p/s/cm2/sr)/(W/cm2)]. IVIS imaging was performed not only to visualize the presence of fluorescent NPs but also to analyze the particle concentration in the organs.

After visualization by IVIS, organs for each treatment sample were submerged in 20-ml Falcon tubes in just enough radioimmunoprecipitation assay (RIPA) lysis buffer (RIPA Lysis and Extraction Buffer, G-Biosciences) to coat the surface of the tissue and homogenized at 30,000 rpm by the IKA handheld homogenizer (IKA Inc., T10 Basic S1, Ultra Turrax, 8000 to 30,000 rpm) until a homogeneous liquid was formed. After all treatment samples were homogenized, fluorescence (RFU) was quantified as described above. All data were analyzed using one-way ANOVA followed by post hoc Tukey.

Isolated RBCs from the 24-hour samples were analyzed by FACS to qualitatively evaluate whether the NPs were adhering to blood cells or being targeted by macrophages in plasma for clearance, if still in circulation at 24 hours. An in vitro assay was constructed first to examine feasibility of this theory before examining in vivo.

For in vitro studies, a 1:10 ratio of NPs/RBCs corresponding to in vivo injections was prepared by mixing each NP treatment with whole mouse blood. First, whole blood was exsanguinated from a wild-type control BALB/c mouse under inhalatory anesthesia for 10 min, combined with the NP treatments, and then centrifuged at 1000g for 10 min to obtain isolated RBCs. These RBCs were then washed using 1 PBS (pH 7.4) three times with centrifugation at 200g for 10 min between each wash. The final samples were each resuspended in 3 ml of 1 PBS (pH 7.4).

For in vivo samples, a representative mouse from the PLGA-DiD, saline, and CAHA 1:2-PLGA-DiD NP treatment groups was selected for examination after 24 hours (blood withdrawal and euthanasia). RBCs were isolated from whole blood withdrawn from each mouse and washed three times in 1 PBS (pH 7.4) as previously described. In addition, supernatant was collected and examined as well for macrophage NP uptake activity. All in vitro and in vivo samples underwent FACS analysis on an LSR II Fortessa flow cytometry machine to examine the detection and location of any NPs (which emitted far-red fluorescence from encapsulated DiD dye) at 670 nm.

After FACS confirmed the presence of NPs adhering onto RBCs both in vitro and in vivo, SEM was performed on these same RBC samples on a Supra55 SEM machine according to the previously established protocol of Brenner et al. (37)

Sera derived from whole blood taken from the final 24-hour in vivo time point after intravenous injection were analyzed using protocol accompanying an ELISA kit to detect IL-6. To conduct the ELISA, 100 l of serum from each treatment group was taken to establish the IL-6 response (Invitrogen Mouse IL-6 Uncoated ELISA Kit with protocol). Absorbance was measured at 450 nm on a 96-well clear ELISA plate using a Spectramax plate reader (Spectramax i3). After acquisition, 4PL statistical fitting was applied to the ELISA mouse IL-6 standard curve, and two-tailed paired t test of the means was applied to assess significance between two treatment groups at a time.

Statistical analyses were conducted using Microsoft Excel 2016 for PK (n = 6) and BD (n = 6) data, which were both analyzed using one-way ANOVA followed by Tukey post hoc test and two-tailed paired t test of the means when interested in cross-verifying significance between two treatment groups. Background buffer autofluorescence was subtracted from all fluorescence-related measurements to account for true sample values. Fluorescence (RFU) was quantified by a SpectraMax i3 plate reader on 200 l of homogenates at the same settings as prior to measure the percentage of NPs relative to the tail vein injection dose. 4PL statistical fitting via RStudio OpenSource was applied to the ELISA mouse IL-6 standard curve, and two-tailed paired t test of the means was applied to assess significance between two treatment groups at a time. All data are presented as means standard error of the mean. DLS is represented as a measure of intensity (%) for size or count for zeta potential. As an internal control, all DLS readings were measured with at least two internal readings/sample/trial. N, P, and statistical tests performed for each experiment are available in its respective figure caption in the text.

Acknowledgments: We thank J. Kim and D. Pan for the training on tail vein intravenous injections for in vivo experiments, M. Nurunnabi for the IVIS training, and D. Pan for the mouse blood for ex vivo experiments. We also thank Z. Zhao and P. Angsantikul for advice and input during the development of the in vivo and ex vivo experiments. We additionally thank the Harvard Center for Nanoscale Systems (CNS) for guidance in experimental development of electron microscopy imaging techniques, the Harvard Bauer Core for usage of flow cytometry instrumentation, and the Wyss Institute for usage of the DLS. We thank M. Goetz, S. D. Pedigo, and R. M. Wadkins for assistance with the SDS-PAGE experiments. Funding: This work was supported by funding from the John A. Paulson School of Engineering and Harvard University and the Sigma Xi Honor Society Student GIAR program. Author contributions: E.E.L.T. conceived the idea. S.M. and E.E.L.T. developed the idea. S.M., C.M.H., and E.E.L.T. developed the experiments. C.M.H. and E.E.L.T. performed the experiments. C.M.H. and E.E.L.T. analyzed the data. E.E.L.T. wrote the paper, with contributions and critical revisions from all coauthors. Competing interests: E.E.L.T. and S.M. are inventors on an invention that covers some aspects of the technology reported in this manuscript (owned and managed by Harvard University). S.M. is a shareholder/consultant/board member of Liquideon LLC, CAGE Bio, and i2O Therapeutics. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors.

Read more from the original source:
Protein-avoidant ionic liquid (PAIL)coated nanoparticles to increase bloodstream circulation and drive biodistribution - Science Advances

Korean study examines the combined impact of aspirin, metformin, and statin’s impact on lung cancer risk – The Cancer Letter

publication date: Sep. 18, 2020

The combined use of aspirin, statins, and metformin is associated with decreased lung cancer incidence and mortality, according to a study published in the Journal of Thoracic Oncology, the journal of the International Association for the Study of Lung Cancer.

All three medications are commonapproximately 35 million people take a statin to control cholesterol; more than 120 million people take metformin to control diabetes and between 6 and 10 million people take aspirin daily.

The aim of this study was to investigate the associations of aspirin, metformin, and statins with lung cancer risk and mortality using population-based nationwide cohort data from The Korean National Health Insurance Services database was used in the present study. The KNHIS is a universal health care system that covers the entire Korean population of 50 million.

To our knowledge, no study has evaluated aspirin, statins, and metformin use and their combined impact on lung cancer incidence and mortality, lead study author Dong Wook Shin, of the Sungkyunkwan University School of Medicine, said in a statement.

Shin and his colleagues (Jihun Kang and Su-Min Jeong) examined 732,199 Koreans from the Korean National Health Insurance Services database. The patients were followed between January 2004 and December 2013. Lung cancer incidence and mortality were identified using a registered lung cancer diagnosis code (ICD-10 code C34) and the Korean National Death Registry.

To address the combined associations of these cardiovascular drugs with lung cancer risk and mortality, the researchers categorized the cohort into eight groups, based on exposure to aspirin, statins, and metformin.

Combined use of aspirin, statins, and metformin was associated with decreased lung cancer incidence (aHR 0.83, 95% CI, 0.690.99) and mortality (aHR 0.83, 95% CI, 0.700.99) compared with non-users.

When these cardiovascular drugs were used in combination, their protective associations with lung cancer risk and related mortality were augmented and the magnitude of effect increased with increasing duration of medication use, Shin said in a statement.

During 2012-2013 (the most recent period in the study), study participants taking all three medications were 3.4% (23,163 out of 676,520).

Interestingly, the inverse association of combined use of aspirin, statins, and metformin was prominent, and the longer the duration of combined use, the more protective the association.

This finding is in line with a study demonstrating that aspirin and metformin synergistically inhibit lung cancer cell proliferation by activating AMP-activated protein kinase, which plays a critical role in regulation of lipogenesis in cancer cells, Shin wrote.

Shin theorized that concomitant use of aspirin, statins, and metformin concurrently inhibits multiple pathways related to lung cancer cell growth and proliferation resulting in favorable associations with lung cancer risk and mortality.

Cigarette smoking associated with worse outcomes for bladder cancer patients after surgery

Patients treated for bladder cancer with a surgery known as radical cystectomy have worse outcomes if they are smokers, according to a systematic review and meta-analysis by Keck Medicine of USC. The study appeared in the Journal of Urology.

This study is important because while it is known that tobacco smoking is the leading cause of bladder cancer, this is the first study to suggest that smoking puts bladder cancer patients at risk after diagnosis, Giovanni Cacciamani, lead author of the study and assistant professor of research urology at the Keck School of Medicine of USC, said in a statement.

More than 500,000 cases of bladder cancer are diagnosed each year worldwide. When the cancer is large or has spread beyond the bladder, patients are typically treated with chemotherapy followed by a radical cystectomy.

Cacciamani and fellow Keck Medicine researchers searched databases to select 17 studies that reported on the impact of tobacco smoking on chemotherapy response and survival outcomes of 13,777 patients following radical cystectomy. Of these patients, 40.8% were active smokers at the time of the surgery, 14.1% former smokers and 45.1% had never smoked or were not smoking at the time of the surgery.

The study showed that active smokers responded worse to chemotherapy and had higher mortality rates, both in general and specifically from bladder cancer, and a higher rate of bladder cancer recurrence than patients who never smoked or were not smoking at the time of surgery.

Former smokers also fared worse in these categories than those who had never smoked, even though the differences were less significant.

The research suggests that as long as a person is not smoking at the time of chemotherapy and surgery, they might do better, Cacciamani said in a statement.

He also recommends that physicians monitor smokers more carefully post-surgery than other patients because they are more at risk for complications or death.

In addition, the study authors recommend that future studies or clinical trials involving bladder cancer chart patients smoking status to create a more accurate picture of what factors affect cancer survival and recurrence.

Other Keck Medicine physicians who authored the study include Mihir Desai, Parkash Gill, Inderbir Gill, and Hooman Djaladat. Saum Ghodoussipour who is a former surgical oncology fellow with Keck Medicine, co-authored the study.

Researchers from medical institutions in Austria, Italy and Russia also participated in the study.

Partner Therapeutics begins phase III study of leukine + ipilumimab and nivolumab front-line melanoma

The EA61411 study conducted by ECOG-ACRIN Cancer Research Group has begun its phase III portion.

Partner Therapeutics Inc. sponsors the study.

EA6141 (NCT02339571) is a randomized controlled study of Leukine (sargramostim, yeast derived rhu-GM-CSF) in combination with ipilimumab and nivolumab for the front line treatment of melanoma.

The restart was based on results of ECOG-ACRINs planned interim efficacy and safety analysis of survival data from the first 250 patients enrolled in the study. FDA granted orphan drug status to Leukine in Sept. 2019, for the potential treatment of stage IIb-IV melanoma.

EA61411 is led by study chair F. Stephen Hodi, director of the Center for Immuno-Oncology at Dana-Farber Cancer Institute and study Co-Chair Ahmad Tarhini, professor of oncologic sciences and director of Cutaneous and Clinical Translational Research at H. Lee Moffitt Cancer Center and Research Institute.

GM-CSF has unique immunomodulatory properties that have the potential to substantially benefit patients with cancer, Hodi said in a statement. He added This study in the front line setting is intended to confirm and broaden the findings in the randomized phase II trial EA1608, which demonstrated improved efficacy and toxicity when sargramostim was added to ipilimumab.

ECOG-ACRIN launched the phase II/III EA6141 study in Sept. 2015. In the study, patients with stage III/IV unresectable melanoma are randomized to receive standard of care treatment with nivolumab and ipilimumab with or without sargramostim. The primary endpoint is overall survival. ECOG-ACRIN planned for the interim trial pause after 240 patients were enrolled, to assess efficacy.

The group paused enrollment in June 2017 and the interim analysis is now complete. Based on the findings of the interim analysis, the ECOG-ACRIN Data Safety Monitoring Committee has given the go ahead to start the enrollment into the phase III portion of the study. The total planned enrollment is 600 patients. The study remains blinded and no data will be released until completion.

The prior data with sargramostim supporting improvement in survival and reduction in immune-related toxicity, as observed in the E1608 study, highlights the importance of further clinical evaluation in combination with checkpoint inhibitors, Tarhini said in a statement.

ECOG-ACRIN previously reported results of Study E1608, a phase II study in which patients with advanced stage melanoma received a combination of sargramostim and ipilimumab or ipilimumab alone2. Among 245 patients, the addition of sargramostim led to longer survival (median 17.5 vs 12.7 months, HR 0.64).

Leukine is not approved for the treatment of melanoma.

Despite progress, adolescents and young adults face substantial cancer disparities by race/ethnicity

A new report examining cancer in adolescents and young adults defined as diagnoses occurring during ages 15 to 39, provides updated estimates of the contemporary cancer burden in this age group, predicting that 89,500 cases and 9,270 deaths will occur in 2020 in the United States. The report appears in CA: A Cancer Journal for Clinicians.

AYAs with cancer are frequently grouped with older or younger patient populations and/or presented in aggregate, masking the wide heterogeneity in cancer occurrence within this population. To address this issue, American Cancer Society investigators also examined cancer incidence, survival, and mortality among AYAs by race/ethnicity and for smaller age groups (15-19, 20-29, and 30-39).

Cancer incidence rates among AYAs are highest in those who are non-Hispanic white (83 per 100,000 population during 2012-2016) and lowest in those who are Asian/Pacific Islander (54 per 100,000 population) for both sexes. This reflects higher rates in non-Hispanic white AYAs for thyroid cancer, testicular tumors, and melanoma compared to other major racial/ethnic groups. Unlike adults ages 40 and older, however, female breast cancer incidence rates in non-Hispanic Black AYAs are 14% higher than those in non-Hispanic white AYAs (25.9 vs 22.3 per 100,000 population).

The authors also note that despite patterns in overall incidence, cancer mortality rates are highest in non-Hispanic Black AYAs, particularly females (12.6 per 100,000 vs 9.2 in non-Hispanic white persons), reflecting substantial survival disparities compared to those who are non-Hispanic white. The largest 5-year cancer-specific survival disparities occur among those who are non-Hispanic Black compared with non-Hispanic whites for acute lymphocytic leukemia (57% vs 71%, respectively) and female breast cancer (78% vs 89%, respectively).

By age group, the cancer incidence rate in AYAs increased during the most recent decade (2007-2016) overall but showed signs of stabilizing among men in their 20s. The rise is largely driven by thyroid cancer incidence rates, which rose by approximately 3% annually among those aged 20 to 39 and 4% among those aged 15 to 19 years. Incidence increased for several cancers linked to obesity, including kidney (3% across all age groups), uterine corpus (3% in group aged 20-39 years), and colorectum (0.9%-1.5% in the group aged 20-39 years).

In contrast to incidence, cancer mortality rates among AYAs for all cancers combined declined in the past decade (2008 through 2017) by 1% across sex and age groups except females aged 30 to 39, among whom rates remained stable due to a flattening of declines in breast cancer mortality. Mirroring incidence, mortality rates increased during the most recent 10 data years (2008-2017) for colorectal and uterine corpus cancers.

Other highlights from the report include:

Adolescents (aged 15-19 years) are more likely to be diagnosed with cancers associated with childhood, such as Hodgkin lymphoma, while those aged 20 to 39 years are more likely to be diagnosed with adult cancers, such as breast. Thyroid cancer is the only cancer predicted to rank among the three most commonly diagnosed cancers in each AYA age group in 2020.

Leukemia continues to be the leading cause of cancer death in ages 15 to 29 years. Among ages 30-39 years, breast (women) and colorectal (men) cancers are the leading cancer causes of death.

Melanoma incidence rates during 2007-2016 rapidly declined in ages 15 to 29 (4%-6% annually, on average). However, among ages 30-39 years, rates declined only slightly among men and remained flat among women.

Overall 5-year relative survival in AYAs for all cancers combined (83%-86% across age groups) is similar to that in children (84%), but masks lower survival for several cancer types, such as acute lymphocytic leukemia (ALL; 60% vs 91%, respectively).

The report notes an increasing body of evidence that tumors in AYAs are molecularly distinct from those in younger or older populations, suggesting differences in etiology and in treatment options. In addition, studies have shown that compared to childhood cancer survivors, AYAs have a higher risk of progression and death from their original cancer. Compared to older cancer patients, AYAs have a higher risk of long-term and late effects including infertility, sexual dysfunction, cardiovascular disease, and other future cancers. However, further research in these areas is needed.

The authors say that progress in reducing cancer morbidity and mortality among AYAs could be improved with more equitable access to health care, as AYAs are more likely than other age groups in the U.S. to be uninsured. Increased clinical trial enrollment, expanded research, and improved awareness among clinicians and patients of early symptoms and signs of cancer could also accelerate progress.

Study: Rubbery properties help RNA nanoparticles target tumors efficiently and quickly leave body

A new study by researchers at The Ohio State University Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard J. Solove Research Institute demonstrated that RNA nanoparticles have elastic and rubbery properties.

These properties explain why these particles target tumors so efficiently and why they possess lower toxicity in animal studies.

RNA nanoparticles show great promise for the targeted delivery of anticancer drugs. Understanding their structure and behavior is essential for their possible future use.

This study, published in the ACS Nano, reveals that RNA nanoparticles have elastic and rubbery properties that enable the molecules to stretch and return to their normal shape. Researchers say that these properties could help the particles target tumors by enabling them to slip through the poorly formed walls of tumor blood vessels and enter a tumor mass.

The researchers further proved that the same rubbery properties enable the RNA nanoparticle to slip through the kidney filters to excrete into the urine half hour after systemic injection, thereby eliminating them from the body relatively quickly. That, in turn, could reduce retention of the anticancer agent in vital organs, lowering an agents toxicity.

We show that RNA nanoparticles have a flexibility that allows for the assembly of molecular structures that have stretchable angles, study leader and corresponding author Peixuan Guo, professor in the College of Pharmacy and the Sylvan G. Frank Endowed Chair in Pharmaceutics and Drug Delivery, said in a statement. Guo also is in the OSUCCC James Translational Therapeutics Research Program.

These findings demonstrate the rubbery properties of RNA nanoparticles and why these molecules hold great promise for industrial and biomedical applications, especially as carriers for targeted delivery of anticancer drugs, Guo, who directs Ohio States Center for RNA Nanobiotechnology and Nanomedicine, said in a statement.

For this study, Guo and colleagues tested the elasticity of nucleic acid polymers by stretching and relaxing individual RNA nanoparticle, while subjecting RNA nanoparticles to elasticity studies using dual-beam optical tweezers built in Guo lab. They used animal models to study the biodistribution, excretion and retention of RNA nanoparticles. This included measuring excretion of the particles in urine, along with the study on the effect of their shape and size.

Key findings include:

RNA nanoparticles are stretchable and shrinkable, like rubber, even after repeated extension and relaxation with multiple repeats by optical tweezers.

In animal models, RNA nanoparticles show stronger cancer targeting and lower accumulation in healthy organs when compared to gold and iron nanoparticles of similar size.

Also in animal models, within half an hour after systemic injection, RNA nanoparticles that were 5, 10 and 20 nm in size were filtered by the kidneys and retained their original structure in urine, even though the upper limit of kidney pore size for filtration is generally 5.5 nm. This suggests that the larger RNA nanoparticles slipped like rubberly and amoeba through filtration pores, then returned to their original size and shape in urine.

Other researchers involved in this study were Chiran Ghimire, Hongzhi Wang, Hui Li, Mario Vieweger and Congcong Xu, The Ohio State University.

Link:
Korean study examines the combined impact of aspirin, metformin, and statin's impact on lung cancer risk - The Cancer Letter

Healthcare Nanotechnology (Nanomedicine) Market Size, Drivers, Potential Growth Opportunities, Competitive Landscape, Trends And Forecast To 2027 -…

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Healthcare Nanotechnology (Nanomedicine) Market Size, Drivers, Potential Growth Opportunities, Competitive Landscape, Trends And Forecast To 2027 -...

Nanomedical Market 2019 | How The Industry Will Witness Substantial Growth In The Upcoming Years | Exclusive Report By MRE – Bulletin Line

The report scope includes detailed competitive outlook covering market shares and profiles key participants in the global Nanomedical market share. Major industry players with significant revenue share include Johnson & Johnson, Mallinckrodt plc., Merck & Company, Inc., Nanosphere, Inc., Pfizer, Inc., Teva Pharmaceutical Industries Ltd., Abbott Laboratories, CombiMatrix Corporation, General electric Company, Sigma-Tau Pharmaceuticals, Inc., and others.

The Nanomedical Market is expected to exceed more than US$ 306 Billion by 2024 at a CAGR of 10.3% in the given forecast period.

Browse Full Report: https://www.marketresearchengine.com/nanomedical-market

Nanomedicine market is mainly driven by increase in acceptance of nanomedicine across diverse applications, rise in government funding & support, emerging technologies for drug delivery, rise in need for therapies with less side effects and allergies, and cost-effectiveness of therapies.

Growing healthcare facilities in developing countries are anticipated to bring numerous opportunities for the growth of nanomedicine market.

Nanomedicine is one of the applications of nanotechnology used in treatment, monitoring, diagnosis, and control of biological systems. Nanomedicine utilizes nanoscale control of materials to improve medicine delivery. Subsequently, nanomedicine has encouraged treatment against different diseases.

The global Nanomedical market is segregated on the basis of Indication as Ophthalmological Diseases, Immunological Diseases, Cardiovascular Diseases, Oncological Diseases, Infectious Diseases, Orthopedic Disorders, Neurological Diseases, Urological Diseases, and Others. Based on Application the global Nanomedical market is segmented in Implants, Regenerative Medicine, Diagnostic Imaging, Drug Delivery, Vaccines, and Others. Based on Modality the global Nanomedical market is segmented in Treatments and Diagnostics.

The global Nanomedical market report provides geographic analysis covering regions, such as North America, Europe, Asia-Pacific, and Rest of the World. The Nanomedical market for each region is further segmented for major countries including the U.S., Canada, Germany, the U.K., France, Italy, China, India, Japan, Brazil, South Africa, and others.

Competitive Rivalry

Johnson & Johnson, Mallinckrodt plc., Merck & Company, Inc., Nanosphere, Inc., Pfizer, Inc., Teva Pharmaceutical Industries Ltd., Abbott Laboratories, CombiMatrix Corporation, General electric Company, Sigma-Tau Pharmaceuticals, Inc., and others are among the major players in the global Nanomedical market. The companies are involved in several growth and expansion strategies to gain a competitive advantage. Industry participants also follow value chain integration with business operations in multiple stages of the value chain.

The Nanomedical Market has been segmented as below:

The Nanomedical Market is segmented on the lines of Nanomedical Market, By Indication, Nanomedical Market, By Application, Nanomedical Market, By Modality, Nanomedical Market, By Region and Nanomedical Market, By Company.

Nanomedical Market, By Indication this market is segmented on the basis of Ophthalmological Diseases, Immunological Diseases, Cardiovascular Diseases, Oncological Diseases, Infectious Diseases, Orthopedic Disorders, Neurological Diseases, Urological Diseases and Others. Nanomedical Market, By Application this market is segmented on the basis of Implants, Regenerative Medicine, Diagnostic Imaging, Drug Delivery, Vaccines and Others. Nanomedical Market, By Modality this market is segmented on the basis of Treatments and Diagnostics. Nanomedical Market, By Region this market is segmented on the basis of North America, Europe, Asia-Pacific and Rest of the World. Nanomedical Market, By Company this market is segmented on the basis of Johnson & Johnson, Mallinckrodt plc., Merck & Company, Inc., Nanosphere, Inc., Pfizer, Inc., Teva Pharmaceutical Industries Ltd., Abbott Laboratories, CombiMatrix Corporation, General electric Company and Sigma-Tau Pharmaceuticals, Inc.

The report covers:

Report Scope:

The global Nanomedical market report scope includes detailed study covering underlying factors influencing the industry trends.

The report covers analysis on regional and country level market dynamics. The scope also covers competitive overview providing company market shares along with company profiles for major revenue contributing companies.

Reasons to Buy this Report:

Request Sample Report from here: https://www.marketresearchengine.com/nanomedical-market

Table of Contents:

4.2.1 Drivers

4.2.2 Restraints

4.2.3 Opportunities

4.2.4 Challenges

4.2 Porters Five Force Analysis

10.1.1 Company Overview

10.1.2 Product/Service Landscape

10.1.3 Financial Overview

10.1.4 Recent Developments

10.2 Mallinckrodt plc.

10.2.1 Company Overview

10.2.2 Product/Service Landscape

10.2.3 Financial Overview

10.2.4 Recent Developments

10.3 Merck & Company, Inc.

10.3.1 Company Overview

10.3.2 Product/Service Landscape

10.3.3 Financial Overview

10.3.4 Recent Developments

10.4 Nanosphere, Inc.

10.4.1 Company Overview

10.4.2 Product/Service Landscape

10.4.3 Financial Overview

10.4.4 Recent Developments

10.5 Pfizer, Inc.

10.5.1 Company Overview

10.5.2 Product/Service Landscape

10.5.3 Financial Overview

10.5.4 Recent Developments

10.6 Teva Pharmaceutical Industries Ltd.

10.6.1 Company Overview

10.6.2 Product/Service Landscape

10.6.3 Financial Overview

10.6.4 Recent Developments

10.7 Abbott Laboratories

10.7.1 Company Overview

10.7.2 Product/Service Landscape

10.7.3 Financial Overview

10.7.4 Recent Developments

10.8 CombiMatrix Corporation

10.8.1 Company Overview

10.8.2 Product/Service Landscape

10.8.3 Financial Overview

10.8.4 Recent Developments

10.9 General electric Company

10.9.1 Company Overview

10.9.2 Product/Service Landscape

10.9.3 Financial Overview

10.9.4 Recent Developments

10.10 Sigma-Tau Pharmaceuticals, Inc.

10.10.1 Company Overview

10.10.2 Product/Service Landscape

10.10.3 Financial Overview

10.10.4 Recent Developments

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Nanomedical Market 2019 | How The Industry Will Witness Substantial Growth In The Upcoming Years | Exclusive Report By MRE - Bulletin Line

What happens when bacteria resist treatment? Trobix lands $3M to protect us from next ‘Super Bug’ – Geektime

Trobix Innovation Ltd. an Israeli-based biotechnology company developing therapies to remove the threat of antimicrobial resistance, announces the closing of a $3 million Series A funding led by its lead investor, Chartered Opus. The funding will be used to advance the company's antimicrobial resistance platform technology and to further the pre-clinical development of its lead product, TBX101, which aims to treat patients carrying gut antimicrobial-resistant bacteria, resulting in antibiotic sensitive gut microbiome.

"I am grateful to Chartered Opus for their confidence in our technology and their trust in our team", said Dr. Adi Elkeles, Founder & CEO of Trobix Bio, which was founded in 2018. "Antimicrobial-resistant threatens to undermine the achievements of modern medicine, and Trobix Bio is committed to developing products that can effectively tackle this imminent threat", he added.

Antimicrobial resistance is a big issue, especially following the outbreak of the COVID-19 pandemic. According to the World Health Organization (WHO), microorganisms such as bacteria, fungi, viruses, and others develop a resistance once introduced to antimicrobial drugs like antibiotics. In light of the Coronavirus, effective treatments become a must, as they affect treatments that become ineffective, further allowing viruses to spread or diseases to take over.

Without a clear solution for the microbial resistance, the BioTech world continues to witness medical procedures such as organ transplants, cancer chemotherapy, diabetes management and major surgery (for example, cesarean sections or hip replacements) become very high risk. Which is not only scary on medical treatment level but also significantly increases healthcare costs, with prolonging hospital stay and more intensive care required. This is exactly where solutions like the one of Trobix Bio comes into play.

"The Covid-19 pandemic stresses the urgent need to tackle the global challenges of infectious diseases, and the global need for a solution to the threat of antimicrobial resistance was there from day one", says Eyal Agmoni, Chairman of Chartered Group. "Trobix Bio is set to revolutionize the landscape of phage-based nanomedicine by introducing its game-changing, precision particle disruptive technology. We are very happy with the progress made by the team and are glad to be part of this unique venture".

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What happens when bacteria resist treatment? Trobix lands $3M to protect us from next 'Super Bug' - Geektime

Cape Breton University researchers hope to help water woes – SaltWire Network

SYDNEY, N.S.

Work taking place at Cape Breton University could help small communities both locally and globally deal with water contamination issues.

Shine (Xu) Zhang is a CBU chemistry professor and holds the Tier II Canada Research Chair in healthy environments and communities and the industrial research chair in applied nanotechnology. He is working on a project that involves electrochemical water treatment which he believes can offer a green, efficient and cost-effective alternative.

Water pollution, water contamination is a global concern but its also a local problem for Cape Breton and Nova Scotia, Zhang said.

He said he wanted to take on water contamination as a research topic because it is such a big issue.

CBU is a local university, but CBU really wants to contribute to the community, Zhang said. The environment is a big issue. Water contamination is also a global issue, therefore, research here, if we do a good job, can not only help local communities but also help people far away from here.

We want to apply what we learn to solve some real-world problems.

His research program aims at exploiting nanotechnology and nanomaterials for environmental and health applications with a focus on water treatment, cancer diagnostics and treatment with precision nanomedicine. Zhang has published 65 journal articles.

He describes the technology hes developed as being relatively simple, with an electrode acting like a filter. One electrode removed organic material while another electrode removed heavy metals.

Water comes through the filter, dirty water becomes clean, Zhang said.

The technology, I feel is useful because, from a research standpoint, energy consumption is very low, so essentially its quite cost-effective. That is compatible, for example, with solar panel, those kinds of various sustainable power source. It can be a very automatic system, so you dont need a lot of manpower to run it.

A request for proposals for a market research consultant issued by CBU recently closed and Zhangs team is currently reviewing the proposals received. It asked for proposals to outline how the consultant would go about understanding and marketing the technology, from lab to market through the successful negotiation of a licence.

Zhang said they are now evaluating the best way to commercialize the technology.

Were looking for different industry partners so that we can do further development of specific products or applications for this to meet different needs, he said. For example, we work with environmental remediation companies, we work with landfill leachate, we work on pharmaceutical wastewater. We want to find industry partners to work on further development.

Its hoped the consultant that they hire will assist in finding those partners. A prototype has been developed.

The ideal starting industry level would be 3,000 litres a day, were about halfway there already, were at about 1,500 litres a day," said Andrew Carrier, who works closely with Zhang.

Carrier noted the technology also works in flows, so you dont need a large quantity of contaminated water to make use of it, and it doesnt take up much physical space. They want the technology to be accessible to as many people who can make use of it as possible, he added.

Its easy to put into a remote location without having to invest much capital, Carrier said.

Zhang noted the technology also doesnt generate any sort of secondary waste as a result of its water treatment.

Zhangs work has been supported by the Atlantic Canada Opportunities Agency, Innovacorp, Springboard Innovation Mobilization program, Nova Scotia Lands as well as CBU.

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Cape Breton University researchers hope to help water woes - SaltWire Network

INBRAIN Neuroelectronics receives funding to push forward the development of graphene-based implants for brain disorders – Graphene-Info

INBRAIN Neuroelectronics, a spin-off of the Catalan Institute of Nanoscience and Nanotechnology (ICN2), the Barcelona Institute of Science and Technology (BIST) and ICREA, has received funding from Sabadell Asabys and Alta Life Sciences, as well as ICF and Finaves, which will allow the company to speed up the development of novel graphene-based implants to optimize the treatment of brain disorders, such as Parkinsons and epilepsy.

INBRAIN Neuroelectronics was established in 2019 with the mission of developing brain-implants based on graphene technology for application in patients with epilepsy, Parkinsons, and other neuronal diseases. These smart devices, built around an innovative graphene electrode, will decode with high certainty neural signals from the brain and produce a therapeutic response adapted to the clinical condition of the specific patient.

The company is designing the least invasive and smartest neural interface that, powered by artificial intelligence and the use of Big Data, will have the ability to read and modulate brain activity, detect specific biomarkers, and trigger adaptive responses to deliver optimal results in personalised neurological therapies. So far, the technology has been validated in in-vitro and in-vivo biocompatibility and toxicity tests and has been successfully used to complete studies on small animals. Recently, INBRAIN began tests on large animals with the aim of ensuring that these graphene devices are safe as well as superior to current solutions based on metals such as platinum and iridium. The company also plans to start human studies soon.

INBRAIN was founded, among others, by ICREA Prof. Jose Garrido, leader of the ICN2 Advanced Electronic Materials and Devices Group, Prof. Kostas Kostarelos, leader of the ICN2 Nanomedicine Group, and Dr. Anton Guimer, a researcher at the Spanish National Centre of Microelectronics (IMB-CNM).

Within the framework of the Graphene Flagship, which is a European macroproject, explains Prof. Garrido, we were able to develop this novel graphene-based technology that will allow measuring and stimulating neuronal activity in the brain with a resolution much higher than that of current commercial technologies.

Throughout 2019, the incorporation of INBRAIN was a priority project for the ICN2 Business and Innovation Department, which coordinated the technology transfer process and successfully orchestrated the licensing of this high-potential technology.

Minimally invasive electronic therapies represent a revolutionary alternative with less potential cost for health systems, comments Carolina Aguilar, CEO of INBRAIN and a former global executive at Medtronic in the field of neuro-stimulation. In our case, the application of new 2D materials such as graphene represents a real opportunity to understand the brain workings in order to optimise and personalize the treatment.

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INBRAIN Neuroelectronics receives funding to push forward the development of graphene-based implants for brain disorders - Graphene-Info

Sirnaomics and Precision NanoSystems Have Formed a Partnership – PRNewswire

Developing and Manufacturing Novel RNAi drug Candidates Using Precision NanoSystems' NxGen Platform

GAITHERSBURG, MD andVANCOUVER, BC, June 17, 2020 /PRNewswire/ - Sirnaomics Inc. (Sirnaomics) and Precision NanoSystems Inc. (PNI) jointly announced a partnership on the development and manufacture of Sirnaomics polypeptide nanoparticle-based RNAi therapeutic product. This strategic joint effort includes the execution of a NanoAssemblr platform license and supply agreement, plus successful production of multiple batches of Sirnaomics drug product candidates, STP705 and STP707, for ongoing IND enabling safety and toxicity studies, as well as several clinical studies.

Sirnaomics is a clinical stage biopharmaceutical company specialized in RNAi-based therapeutics for addressing the unmet needs in treatment of cancers and fibrosis diseases. The company has developed proprietary polypeptide nanoparticle carriers for efficient siRNA delivery, to advance an enriched drug product pipeline. Sirnaomics' lead product candidate, STP705, is an siRNA (small interfering RNA) therapeutic which takes advantage of a dual-targeted inhibitory property together with a polypeptide nanoparticle (PNP)-enhanced delivery to directly knock down both TGF-1 and COX-2 gene expression. The product candidate has received multiple IND approvals from both the US FDA and Chinese NMPA, including treatments of Cholangiocarcinoma, Non-Melanoma skin cancer and Hypertrophic Scar. STP705 has also received Orphan Drug Designation for treatment of Cholangiocarcinoma, Primary Sclerosing Cholangitis and Hepatocellular Carcinoma. A recent interim analysis report of a phase IIa clinical study on STP705 for treatment of Squamous Cell Carcinoma in situ indicated the topline therapeutic results with complete histological clearance tumor cell on treated sites. Using the same dual targets design, Sirnaomics has further developed STP707, a systemic formulation with broader application potential.

Sirnaomics' founder, president and CEO, Dr. Patrick Lu said, "As the leader in RNAi therapeutics specialized in polypeptide nanoparticle formulation, we are so excited to see the further advancement of our process development and large scale product manufacturing, using PNI's NxGen microfluidic technology. In working with PNI's team and the NanoAssemblr platform, we were able to establish a robust manufacturing process from a nominated drug candidate to GMP manufacturing in just a few months, greatly accelerating our drug development process". Sirnaomics is currently using these batches produced with NxGen for non-human primate safety toxicity studies and clinical studies."

PNI is a global leader in technology solutions to enable the development and manufacture of new nanomedicines in the areas of vaccines, cell therapies and gene therapies for the treatment of oncology, infectious diseases, and rare diseases. With the NanoAssemblr suite of products, PNI provides solutions across the drug development process for clients to develop and seamlessly scale their drug programs. Dr. James Taylor, co-founder and CEO of PNI said, "We are pleased to support Sirnaomics, an innovative RNAi therapeutics company, with our NanoAssemblr platform and Clinical Solutions Team that helped take their drug program to a successful GMP batch manufacture. We believe the NanoAssemblr microfluidic technology enables exquisite control over the particle size, charge and encapsulation efficiency which was important for the performance of Sirnaomics' drug product candidates." PNI's NanoAssemblr platform, with over 400 systems placed worldwide, is designed to enable drug developers to rapidly progress from R&D to industrial-scale nanomedicine manufacture.

About SirnaomicsSirnaomics, Inc., a leading privately held biopharmaceutical company for discovery and development of RNAi therapeutics, is a Delaware corporation headquartered in Gaithersburg, Maryland, USA, with subsidiaries in Suzhou and Guangzhou, China. The Company's mission is to develop novel therapeutics to alleviate human suffering and advance patient care in areas of high unmet medical need. The guiding principles of the company are: Innovation, Global Vision with a Patient Centered focus. Members of the senior management team have a great deal of combined experience in the biopharmaceutical industry, financial, clinical and business management in both the USA and China. The company is supported by funding from institutional investors, corporate partnerships and government grants. Sirnaomics has developed a strong portfolio of intellectual property with an enriched product pipeline. The therapeutic areas of focus include oncology and anti-fibrotic therapeutics. Learn more at http://www.sirnaomics.com.

About Precision NanoSystems Inc.Precision NanoSystems Inc. (PNI) proprietary NanoAssemblr Platform enables the rapid, reproducible, and scalable manufacture of next generation nanoparticle formulations for the targeted delivery of therapeutic and diagnostic agents to cells and tissues in the body. PNI provides instruments, reagents and services to life sciences researchers, including pharmaceutical companies, and builds strategic collaborations to revolutionize healthcare through nanotechnology. For more information visithttp://www.precisionnanosystems.com.

SOURCE Precision Nanosystems

http://www.precisionnanosystems.com

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Sirnaomics and Precision NanoSystems Have Formed a Partnership - PRNewswire

Semiconductor-laced bunny eyedrops appear to nuke infections – The Register

Don't worry, little guy. They're really, really small!

In early lab experiments on rabbits, eyedrops laced with nanoparticles appear to combat bacterial keratitis, a serious infection of the cornea which can, in severe cases, cause blindness.

Researchers hope that these nanoparticles could someday offer a non-toxic alternative to antibiotics, which have the undesirable side effect of creating resistant bacteria.

A common treatment option is steroids, but they can cause scarring. Boffins have found that some nanomaterials, such as copper oxide and silicon, appear to damage bacterial cells. Lately, some groups have realised that carbon quantum dots really tiny semiconductors seem to offer similar benefits with low toxicity, the ability to disperse in water easily, and a relatively simple fabrication process.

"We think it should be safe," Han-Jia Lin, a biochemist at National Taiwan Ocean University in Keelung, told The Register. He and his team had previously studied quantum dots for wound healing in rats.

In the new study, Lin and his team created carbon quantum dots approximately six nanometers in diameter by heating spermidine at around 200oC for about three hours and placing the resultant dots in liquid. The ratio was about 0.4 per cent quantum dot to liquid.

The team infected rabbits with bacterial keratitis. Some received 4 per cent SMX antibiotics, some the quantum-filled eye drops, and others no treatment for control. The researchers found that the quantum dot eyedrop solution showed therapeutic effects right away, even after the first day. The dots were small enough to sneak into the cornea and destroy the bacterial cells.

This had something to do with the quantum dots' compatibility with the cells as well as how they destabilised the cell membranes. The researchers don't know exactly why they work.

By two weeks, the rabbits' eyes were mostly better the quantum dot eyedrop worked about as well as antibiotics. Lin says the treated rabbits showed no side effects from treatment.

A paper describing the research appeared this week in ACS Nano.

It's a "conceptually and technically quite elegant study with remarkable results" but "still with a couple of open questions and obvious risks before this could lead to any product that could help patients," Claus-Michael Lehr, a nanomedicine researcher at Saarland University in Saarbrcken, Germany, told The Reg.

First, he said the reasons why the nanomedicine has such strong bactericidal effects is "not easily explained". Second, the effect of opening tight junction tissue barriers (a potential risk in itself) needs to be shown to be reversible. Third, what chemical products are formed by the quantum dots are they toxic or carcinogenic?

Finally, he said it was wasn't clear how quantum dots that penetrate tissue would behave in the long term. "These structures are probably not biodegradable," he said, "and if they were, what metabolites are being formed?"

Lin says the next steps are to test the long-term effects of the quantum dots, but the the team is trying to be careful in their research to try to limit how they accumulate in bodies. Here, for example, they tested them on the eye.

Because the carbon quantum dots work on such a sensitive part of the body such as the eye without apparently harming cells, "This has potential," Lin said.

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Semiconductor-laced bunny eyedrops appear to nuke infections - The Register

Nanomedicine Market Analysis and Opportunities Assessment, Product types and Application, Regional outlook, Leading players during the Forecast period…

The Global Nanomedicine Market Professional Survey Report 2019 report mainly includes the major company profiles with their annual sales & revenue, business strategies, company major products, profits, industry growth parameters, industry contribution on global and regional level. This report covers the global Nanomedicine Market performance in terms of value and volume contribution. This section also includes major company analysis of key trends, drivers, restraints, challenges, and opportunities, which are influencing the global Nanomedicine Market. Impact analysis of key growth drivers and restraints, based on the weighted average model, is included in this report to better equip clients with crystal clear decision-making insights.

Major Players in Nanomedicine market are:Company 1Company 2Company 3Company 4Company 5Company 6Company 7Company 8Company 9

Most important types of Nanomedicine products covered in this report are:Type 1Type 2Type 3Type 4Type 5

Most widely used downstream fields of Nanomedicine market covered in this report are:Application 1Application 2Application 3Application 4Application 5

Overview of the Report:The report begins with a market overview and moves on to cover the growth prospects of the Nanomedicine markets. Global Nanomedicine industry 2019 is a comprehensive, professional report delivering market research data that is relevant for new market entrants or established players. Key strategies of the companies operating in the markets and their impact analysis have been included in the report. Furthermore, a business overview, revenue share, and SWOT analysis of theleading players in the Nanomedicine market are available in the report.

Nanomedicine Market: Regional Analysis Includes:

Nanomedicine Market Report contents include:

Reasons for purchasing Nanomedicine Market Report:

1. To provide detailed analysis of the market structure along with forecast of the various segments and sub-segments of the global Nanomedicine Market.

2. To provide insights about factors affecting the market growth. To analyze the Nanomedicine Market based on various factors price analysis, supply chain analysis, porter five force analysis etc.

3. To provide historical and forecast revenue of the Nanomedicine Market segments and sub-segments with respect to four main geographies and their countries-North America, Europe, Asia, and Rest of the World.

4. Country level analysis of the market with respect to the current market size and future prospective.

5. To provide country level analysis of the market for segment by application, product type and sub-segments.

6. To provide strategic profiling of key players in Nanomedicine market, comprehensively analyzing their core competencies, and drawing a competitive landscape for the market.

7. Track and analyze competitive developments such as joint ventures, strategic alliances, mergers and acquisitions, new product developments, and research and developments in the global Nanomedicine Market.

(*If you have any special requirements, please let us know and we will offer you the report as you want.)

Contact Us:Web:www.qurateresearch.comE-mail:sales@qurateresearch.comPh: US +13393375221, IN +919881074592

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Cancer Stem Cells as Preferential Target for Personalized Cancer Nanomedicine – Video


Cancer Stem Cells as Preferential Target for Personalized Cancer Nanomedicine
Chair: Prof. Dr. Jan Mollenhauer, NanoCAN, University of Southern Denmark, Odense (DK) Session: Targeted and Personalized Cancer Nanomedicine 2 Speaker: Prof...

By: TAUVOD

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Cancer Stem Cells as Preferential Target for Personalized Cancer Nanomedicine - Video

Scientists Devise New Platform to Overcome the Limits of MRI Contrast Agents – Scicasts (press release) (blog)

Daejeon, Korea (Scicasts) A research team led by CHEON Jinwoo at the Center for Nanomedicine, within the Institute for Basic Science (IBS), developed the Nano MRI Lamp: A new technology platform that tunes the magnetic resonance imaging (MRI) signals "ON" only in the presence of the targeted disease.

Published in Nature Materials, this study can overcome the limitations of existing MRI contrast agents.

MRI is an increasingly popular non-invasive technique for diagnosis and, importantly, does not use harmful radiation. Some tissues show a natural contrast on MRI, but for some specific types of imaging, patients are administered a MRI contrast agent to enhance the difference between the target area and the rest of the body. "Typical MRI contrast agents, like gadolinium, are injected in an "ON" state and distributed across the whole biological system with relatively large background signal," explains Director Cheon. "We found a new principle to switch the MRI contrast agent "ON" only in the location of the target." IBS scientists discovered how to switch the signal ON/OFF by using the Nano MRI Lamp.

The Nano MRI Lamp technology consists of two magnetic materials: A quencher (magnetic nanoparticle) and an enhancer (MRI contrast agent). The switch is due to the distance between the two. When the two materials are at a critical distance, farther than 7 nanometers (nm), the MRI signal is "ON", whereas when they are placed closer than 7 nm, the MRI signal is "OFF". The researchers named this phenomenon Magnetic REsonance Tuning (MRET), which is analogous to the powerful optical sensing technique called Fluorescence Resonance Energy Transfer (FRET).

The researchers tested the Nano MRI Lamp for cancer diagnosis. They detected the presence of an enzyme that can induce tumour metastasis, MMP-2 (matrix metalloproteinase-2) in mice with cancer. They connected the two magnetic materials with a linker that is naturally cleaved by MMP-2. Since the linker keeps the two materials close to each other, the MRI signal was "OFF". However, in the presence of the cancer, the linker is cleaved by MMP-2, which cause the two materials to be separated and the MRI signal switched "ON". Therefore, the MRI signal indicated the location of MMP-2, and the tumour. The scientists also found that the brightness of the MRI signal correlates with the concentration of MMP-2 in the cancerous tissue.

Most importantly, the Nano MRI Lamp remains switched off until it meets a biomarker associated with a specific disease, allowing higher sensitivity. "The current contrast agent is like using a flashlight during a sunny day: Its effect is limited. Instead, this new technology is like using a flash light at night and therefore more useful," explains Cheon.

Beyond cancer diagnosis, the Nano MRI Lamp can, in principle, be applied to investigate a variety of biological events, such as enzymolysis, pH variation, protein-protein interactions, etc. IBS scientists expect that it would be useful for both in vitro and in vivo diagnostics.

"Although we still have a long way to go, we established the principle and believe that the MRET and Nano MRI Lamp can serve as a novel sensing principle to augment the exploration of a wide range of biological systems," concludes Cheon. The research group is now working on developing safer and smarter multitasking contrast agents, which can simultaneously record and interpret multiple biological targets, and eventually allow a better understanding of biological processes and accurate diagnosis of diseases.

Article adapted from a Institute for Basic Science news release.

Publication: Distance-dependent magnetic resonance tuning as a versatile MRI sensing platform for biological targets. Jin-sil Choi et al. Nature Materials (February 06, 2017): Click here to view.

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Scientists Devise New Platform to Overcome the Limits of MRI Contrast Agents - Scicasts (press release) (blog)