What’s the next big thing from Israel? Bio-convergence – ISRAEL21c

Testing new cancer drugs on 3D-printed tumor cells. Analyzing the gut microbiome to determine the best medicine for Crohns disease. Identifying genetic pairs so that a drug can turn off a cancer cell.

These are just a few of the overlaps of biology, physics, computer science, mathematics, engineering, materials science and nanotechnology that make up the new field of bio-convergence.

The Israel Innovation Authorityis betting on bio-convergence as the next big thing from the Startup Nation.

Israel to invest NIS 100 million in bio-convergence

The IIA announced in January that it would invest up to about $30 million in bio-convergence technologies and companies. In July, the governmental agency added a call for R&D proposals from academia and industry in the field of bio-convergence with a budget of $4 million.

In August, a third call for bio-convergence proposals this time for collaboration between Israeli and South Korean companies came with a $4.16 million budget and a plan to provide grants up to 50 percent of R&D expenses.

The bio-convergence push is a bit of a departure for the IIA.

We usually work in a bottom up approach and very seldom intervene and select a specific technological field for strategic investments, Anya Eldan, vice president of the IIAs Startup Division, tells ISRAEL21c. In the past it has been cyber and fintech. Now weve identified bio-convergence as the next growth engine for the Israeli economy.

Anya Eldan, vice president of the IsraelInnovation Authoritys Startup Division. Photo: courtesy

Developing disease-fighting drugs the old-fashioned way takes decades and billions of dollars. The new era of pharma will see researchers from multiple disciplines working together.

When we started to look for the next growth engine, we realized that none of the major pharmaceutical companies are invested in bio-convergence, Eldan explains. Theyre looking at biology but theyre not sure how to approach it.

Israel, however, is a small country where everyone knows one another, making it relatively easy to put together multidisciplinary teams.

On a folksier level, Eldan says Israelis large Friday night Shabbat dinners naturally foster collaboration. People have to find things to talk about. So, a doctor mentions at the dinner table he has a patient without a solution and the engineer in the family says, That shouldnt be, and from there a startup is born.

This trend could have a major impact on the global healthcare system crisis. Health expenditures worldwide were expected to reach $10 trillion by 2022even before the advent of Covid-19. Half the US population is considered chronically ill, accounting for some 85% of the total expenditure on healthcare services.

Unlocking academic research

The IIA has identified approximately 80 companies working in the field of bio-convergence. Much of the knowhow is tucked away in Israels academic centers.

Ronit Satchi Fainaro is a prime example.

Named Woman of the Year by the Israeli business publication Globes in 2019, Satchi Fainaro heads the 30-person cancer research and nano-medicine laboratory in the department of physiology and pharmacology at Tel Aviv University.

Satchi Fainaros lab includes research associates in biology, chemistry, medical engineering, bioinformatics and even an architecture student, she tells ISRAEL21c. We are living in the post-genomic era, so theres a lot of room for computer science.

Satchi Fainaros lab developed a method for 3D printing cancerous brain tumors using MRI on images.

We do the image analysis and convert it to a file that a 3D printer can read. Then we create a 3D-printed tumor its like a Mini-Me of that tumor, she says, referring to the Mike Meyers character from the Austin Powers films.

Satchi Fainaros lab creates not one but up to 20 mini-tumors, which are then connected to a set of tubes and pumps that deliver simulated blood and most importantly chemotherapy or other cancer treatments. That allows physicians to test drugs on a perfect copy of the actual tumor.

Satchi Fainaro is also working on an immunotherapy nano-vaccine for melanoma and an immune-modulated response against Covid-19.

Sequencing the microbiome

Jonathan Solomon and Assaf Oron are the CEO and chief business development officer, respectively, of BiomX, another Israeli bio-convergence pioneer.

BiomX is working on a treatment for Crohns and other inflammatory bowel diseases by sequencing the bacteria in a patients microbiome in order to deliver a gut-punch to the exact bacteria causing symptoms.

BiomXs technology is based on the hypothesis that these diseases are driven by the microbiome and that specific bacteria seem to be pro-inflammatory and antibiotic resistant, Solomon tells ISRAEL21.

Bacteriophage image courtesy of BiomX

Bio-convergence techniques assure that a patient receives the right phages a type of virus that infects bacteria to kill only the offending microbes.

Antibiotics are very indiscriminate killers, Solomon says, which leads to the killing of both harmful and beneficial bacteria and, in many cases, the development of antibiotic-resistant bacteria. Phages are very precise. There are no side effects.

Beyond IBD, acne and liver disease are next on BiomXs list. Even cancer is a possibility.

BiomXs technology was initially developed and licensed from the Weizmann Institute in Rehovot. The company has 100 employees and is publicly traded in the United States.

Synthetic lethality

Then theres Pangea, whose bio-convergence niche is synthetic lethality.

Its a very simple notion with a confusing name, CTO Tuvik Beker tells ISRAEL21c.

The basic idea is that genes often act in pairs. If a gene is acting unnaturally in a tumor (for example, it may be shut down due to mutation or abnormal expression), identifying and shutting down the genes partner can selectively kill the malignant cells.

Pangea brings the computational element.

If there are 20,000 genes in the human genome, simple math means there are about 400 million gene pairs, Beker explains. To test all these pairs for synthetic lethality is very challenging.

As a result, most companies restrict themselves to a couple of hundred genes that they know are important in cancer. Pangea, by contrast, looks for paired genes that are vulnerable to collateral damage, not just the ones driving the tumor, Beker says.

The Tel Aviv-based company hopes to launch its service commercially as early as 2021 with a focus on providing personalized treatment recommendations.

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Nanorobotics Market Research, Growth Opportunities, Analysis and Forecasts Report 2020-2026 – The Think Curiouser

AllTheResearchs published a research report on the Nanorobotics market, which represents a study for the period from 2020 to 2026. The research provides a near look at the market scenario and dynamics impacting its growth. This report highlights the crucial developments along with other events happening in the market which are marking on the growth and opening doors for future growth in the coming years. Additionally, the report is built based on the macro- and micro-economic factors and historical data that can influence the growth.

The global Nanorobotics market was valued at US$ 5.11 Bn in 2018 and is expected to reach US$ 10.71 Bn in 2026, growing at a CAGR of 9.9% during the forecast period.

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The global Nanorobotics market has been comprehensively analyzed and the different companies that occupy a large percentage of the market share in the regions mentioned have been listed out in the report. Industry trends that are popular and are causing a resurgence in the market growth are identified. A strategic profile of the companies is also carried out to identify the various subsidiaries that they own in the different regions and who are responsible for daily operations in these regions.

The Key Players Covered in Nanorobotics Market Study are:

How Report will help you to make decisions for business:

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Nanorobotics market is split by Type and by Application. For the period 2015-2026, the growth among segments provide accurate calculations and forecasts for sales by Type and by Application in terms of volume and value. This analysis can help you expand your business by targeting qualified niche markets.

Market Segmentation by Type:

Market Segmentation by Applications:

COVID-19 Impact on Nanorobotics Market:

The outbreak of COVID-19 has brought along a global recession, which has impacted several industries. Along with this impact COVID Pandemic has also generated few new business opportunities for Nanorobotics Market. Overall competitive landscape and market dynamics of Nanorobotics has been disrupted due to this pandemic. All these disruptions and impacts has been analysed quantifiably in this report, which is backed by market trends, events and revenue shift analysis. COVID impact analysis also covers strategic adjustments for Tier 1, 2 and 3 players of Nanorobotics Market.

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AllTheResearch was formed with the aim of making market research a significant tool for managing breakthroughs in the industry. As a leading market research provider, the firm empowers its global clients with business-critical research solutions. The outcome of our study of numerous companies that rely on market research and consulting data for their decision-making made us realise, that its not just sheer data-points, but the right analysis that creates a difference.While some clients were unhappy with the inconsistencies and inaccuracies of data, others expressed concerns over the experience in dealing with the research-firm. Also, same-data-for-all-business roles was making research redundant. We identified these gaps and built AllTheResearch to raise the standards of research support.

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Coronavirus nanoscience: the tiny technologies tackling a global pandemic – Reaction

The world-altering coronavirus behind the COVID-19 pandemic is thought to be just 60 nanometres to 120 nanometres in size. This is so mind bogglingly small that you could fit more than 400 of these virus particles into the width of a single hair on your head. In fact, coronaviruses are so small that we cant see them with normal microscopes and require much fancier electron microscopes to study them. How can we battle a foe so minuscule that we cannot see it?

One solution is to fight tiny with tiny. Nanotechnology relates to any technology that is or contains components that are between 1nm and 100nm in size. Nanomedicine that takes advantage of such tiny technology is used in everything from plasters that contain anti-bacterial nanoparticles of silver to complex diagnostic machines.

Nanotechnology also has an impressive record against viruses and has been used since the late 1880s to separate and identify them. More recently, nanomedicine has been used to develop treatments for flu, Zika and HIV. And now its joining the fight against the COVID-19 virus, SARS-CoV-2.

Diagnosis

If youre suspected of having COVID, swabs from your throat or nose will be taken and tested by reverse transcription polymerase chain reaction (RT-PCR). This method checks if genetic material from the coronavirus is present in the sample.

Despite being highly accurate, the test can take up to three daysto produce results, requires high-tech equipment only accessible in a lab, and can only tell if you have an active infection when the test is taken. But antibody tests, which check for the presence of coronavirus antibodies in your blood, can produce results immediately, wherever youre tested.

Antibodies are formed when your body fights back against a virus. They are tiny proteins that search for and destroy invaders by hunting for the chemical markers of germs, called antigens. This means antibody tests can not only tell if you have coronavirus but if you have previously had it.

Antibody tests use nanoparticles of materials such as gold to capture any antibodies from a blood sample. These then slowly travel along a small piece of paper and stick to an antigen test line that only the coronavirus antibody will bond to. This makes the line visible and indicates that antibodies are present in the sample. These tests are more than 95% accurate and can give results within 15 minutes.

Vaccines and treatment

A major turning point in the battle against coronavirus will be the development of a successful vaccine. Vaccines often contain an inactive form of a virus that acts as an antigen to train your immune system and enable it develop antibodies. That way, when it meets the real virus, your immune system is ready and able to resist infection.

But there are some limitations in that typical vaccine material can prematurely break down in the bloodstream and does not always reach the target location, reducing the efficiency of a vaccine. One solution is to enclose the vaccine material inside a nanoshell by a process called encapsulation.

These shells are made from fats called lipids and can be as thin as 5nm in diameter, which is 50,000 times thinner than an egg shell. The nanoshells protect the inner vaccine from breaking down and can also be decorated with molecules that target specific cells to make them more effective at delivering their cargo.

This can improve the immune response of elderly people to the vaccine. And critically, people typically need lower doses of these encapsulated vaccines to develop immunity, meaning you can more quickly produce enough to vaccinate an entire population.

Encapsulation can also improve viral treatments. A major contribution to the deaths of virus patients in intensive care is acute respiratory distress syndrome, which occurs when the immune system produces an excessive response. Encapsulated vaccines can target specific areas of the body to deliver immunosuppressive drugs directly to targeted organs and helping regulate our immune system response.

Transmission reduction

Its hard to exaggerate the importance of wearing face masks and washing your hands to reducing the spread of COVID-19. But typical face coverings can have trouble stopping the most penetrating particles of respiratory droplets, and many can only be used once.

New fabrics made from nanofibres 100nm thick and coated in titanium oxide can catch droplets smaller than 1,000nm and so they can be destroyed by ultraviolet (UV) radiation from sunlight. Masks, gloves and other personal protective equipment (PPE) made from such fabrics can also be washed and reused, and are more breathable.

Another important nanomaterial is graphene, which is formed from a single honeycomb layer of carbon atoms and is 200 times stronger than steel but lighter than paper. Fabrics laced with graphene can capture viruses and block them from passing through. PPE containing graphene could be more puncture, flame, UV and microbe resistant while also being light weight.

Graphene isnt reserved for fabrics either. Nanoparticles could be placed on surfaces in public places that might be particularly likely to facilitate transmission of the virus.

These technologies are just some of the ways nanoscience is contributing to the battle against COVID-19. While there is no one answer to a global pandemic, these tiny technologies certainly have the potential to be an important part of the solution.

Josh Davies is a PhD Candidate in Chemistry at Cardiff University.

This article was originally published in The Conversation.

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Coronavirus nanoscience: the tiny technologies tackling a global pandemic - Reaction

Nanomedicine Seen As A Promising Approach For Diagnosis and Treatment Against COVID – PRNewswire

PLAM BEACH, Fla., Sept. 16, 2020 /PRNewswire/ --The National Institute for Health (NIH) is at the heart of the emerging and rapidly evolving war against the global pandemic. They constantly update the public on the latest information on research for a vaccine and therapies to fight the virus. A recent report from them shone the light on a specific promising therapeutic approach nanomedicine. The NIH said that nanomedicine is a promising approach fordiagnosis, treatment and prophylaxis against COVID-19. They said that: "The COVID-19pandemic caused by the newly emerged severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) puts the world in an unprecedented crisis, leaving behind huge human losses and deep socioeconomic damages. Due to the lack of specific treatment against SARS-CoV-2, effective vaccines and antiviral agents are urgently needed to properly restrain the COVID-19 pandemic. Repositioned drugs such asremdesivir have revealed a promising clinical efficacy against COVID-19. Interestingly, nanomedicine as a promising therapeutic approach could effectively help win the battle between coronaviruses and host cells."Mentioned in today's commentary include: NanoViricides, Inc. (NYSE: NNVC), Immunomedics(NASDAQ: IMMU), Gilead Sciences, Inc. (NASDAQ: GILD), Inovio Pharmaceuticals, Inc. (NASDAQ: INO), Novavax, Inc. (NASDAQ: NVAX).

Due to a lack of approved vaccines and specific treatments only preventive measures can currently be applied. Currently, development of an effective vaccine and specific treatment is the main concern for researchers worldwide to fight the current COVID-19 and any future mutations. Understanding the coronaviral genome and the processes of viral replication and pathogenesis will enable researchers to develop specific drugs and vaccines. So researchers are turning to nanomedicine, one of the most important and emerging fields of modern science.

NanoViricides, Inc. (NYSE American: NNVC) Breaking News: NanoViricides Nominates a Novel Candidate for Advancing Into Clinical Trials for Treatment of COVID-19 NanoViricides, a global leader in the development of highly effective antiviral therapies based on a novel nanomedicines platform, today announced that it has nominated a clinical drug candidate for the treatment of COVID-19, thus further advancing its COVID-19 program closer to human clinical trials.

The Company has accelerated its drug development program for COVID-19 with the goal of creating the most effective medicine to obtain regulatory approval for emergency use in the COVID-19 pandemic in the shortest timeline feasible, after achieving proof of concept of broad-spectrum anti-coronavirus effectiveness of test candidates. The Company therefore aggressively worked to harness the full power of the nanoviricides nanomedicine platform to achieve these objectives.

A curative treatment for a virus such as SARS-CoV-2 coronavirus would require a multi-faceted attack that shuts down (i) ability of the virus to infect host cells and simultaneously, (ii) ability of the virus to multiply inside the host cells. The nanoviricide platform enables direct multi-point attack on the virus that is designed to disable the virus and its ability to infect new cells. At the same time, a nanoviricide is also capable of carrying payload in its "belly" (inside the micelle) that can be chosen to affect the ability of the virus to replicate. The nanoviricide is designed to protect the payload from metabolism in circulation. Thus, the nanoviricide platform provides an important opportunity to develop a curative treatment against SARS-CoV-2, the cause of COVID-19 spectrum of pathologies.

The clinical candidate the Company has chosen is identified as NV-CoV-1-R. It is made up of a nanoviricide that we have found to possess broad-spectrum anti-coronavirus activity, now identified as NV-CoV-1, and remdesivir encapsulated inside the core of NV-CoV-1. NV-CoV-1 itself is designed to attack the virus particles themselves, and possibly would also attack infected cells that display the virus antigen S-protein, while sparing normal (uninfected) cells that do not display the S-protein. Additionally, remdesivir is widely understood to attack the replication cycle of the virus inside cells. Thus the combined attack enabled by NV-CoV-1-R on the virus could prove to be a cure for the infection and the disease, provided that the necessary dosage level can be attained without undue adverse effects. Human clinical trials will be required to determine the safety and effectiveness of NV-CoV-1-R.

Remdesivir is a well-known antiviral drug (developed by Gilead) that has been approved for emergency use treatment of SARS-CoV-2 infection or COVID-19 in several countries. NV-CoV-1 is a novel agent that is being used as an adjuvant to remdesivir in creating NV-CoV-1-R, to improve the overall effectiveness. It is well known that remdesivir suffers from rapid metabolism in circulation that breaks down the prodrug to its nucleoside form which is not readily phosphorylated. The Company anticipates that encapsulation in NV-CoV-1 may protect remdesivir from this rapid metabolism. If this happens, the effective level and stability of remdesivir in the body would increase. This increase may lead to increased effectiveness if there are no adverse effects. Such increased effectiveness, if found, may also allow reduction in the required dosage of remdesivir in the encapsulated form, i.e. as NV-CoV-1-R. In this sense, NV-CoV-1 can be viewed to act as an adjuvant that enhances the effect of remdesivir, a known antiviral against SARS-CoV-2.

"This is an extremely important milestone for the Company," said Anil R. Diwan, PhD, President and Executive Chairman of the Company, adding, "We look forward to rapid development of the IND enabling core safety pharmacology studies and, thereafter, human clinical development on an accelerated timeline in these trying times of the pandemic." Read the full press release by going to: http://www.nanoviricides.com/companynews.html

In other biotech news in the markets this week:

Immunomedics(NASDAQ: IMMU) and Gilead Sciences, Inc. (NASDAQ: GILD)recently announcedthat the companies have entered into a definitive agreement pursuant to which Gilead will acquire Immunomedics for $88.00 per share in cash. The transaction, which values Immunomedics at approximately $21 billion, was unanimously approved by both the Gilead and Immunomedics Boards of Directors and is anticipated to close during the fourth quarter of 2020.

The agreement will provide Gilead with TrodelvyTM(sacituzumab govitecan-hziy), a first-in-class Trop-2 directed antibody-drug conjugate (ADC) that was granted accelerated approval by the U.S. Food and Drug Administration (FDA) in April for the treatment of adult patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease. Immunomedics plans to submit a supplemental Biologics License Application (BLA) to support full approval of Trodelvy in the United States in the fourth quarter of 2020. Immunomedics is also on track to file for regulatory approval in Europe in the first half of 2021.

"This acquisition represents significant progress in Gilead's work to build a strong and diverse oncology portfolio. Trodelvy is an approved, transformational medicine for a form of cancer that is particularly challenging to treat. We will now continue to explore its potential to treat many other types of cancer, both as a monotherapy and in combination with other treatments," said Daniel O'Day, Chairman and Chief Executive Officer, Gilead Sciences. "We look forward to welcoming the talented Immunomedics team to Gilead so we can continue to advance this important new medicine for the benefit of patients with cancer worldwide."

INOVIO (NASDAQ: INO), a biotechnology company focused on bringing to market precisely designed DNA medicines to treat and protect people from infectious diseases and cancer, recently announced that Thermo Fisher Scientific, the world leader in serving science, has signed a letter of intent to manufacture INOVIO's DNA COVID-19 vaccine candidate INO-4800.

Thermo Fisherjoins other contract development and manufacturing organizations in INOVIO's global manufacturing consortium, enabling INOVIO to potentially scale commercial production of INO-4800. With its consortium of third-party manufacturers, INOVIO plans to have 1001million doses of INO-4800 manufactured in 2021, subject to FDA approval of INO-4800 for use as a COVID-19 vaccine.Thermo Fisherplans to manufacture INO-4800 drug substance as well as perform fill and finish of INO-4800 drug product at its commercial facilities in the US. At peak capacity,Thermo Fisherprojects that it could produce at least 100 million doses of INO-4800 annually.

Novavax, Inc. (NASDAQ: NVAX), a late-stage biotechnology company developing next-generation vaccines for serious infectious diseases, recently announced an amendment to its existing agreement with Serum Institute of India Private Limited (SIIPL) under which SIIPL will also manufacture the antigen component of NVXCoV2373, Novavax' COVID19 vaccine candidate. With this agreement, Novavax increases its manufacturing capacity of NVX-CoV2373 to overtwo billion doses annually, when all planned capacity has been brought online by mid-2021. NVXCoV2373 is a stable, prefusion protein made using Novavax' recombinant protein nanoparticle technology and includes Novavax' proprietary MatrixM adjuvant.

"Today's agreement with Serum Institute enhances Novavax' commitment to equitable global delivery of our COVID-19 vaccine. With this arrangement, we have now put in place a global supply chain that includes the recently acquired Praha Vaccines and partnerships with leading biologics manufacturers, enabling production on three continents," said Stanley C. Erck, President and Chief Executive Officer of Novavax. "We continue to work with extraordinary urgency to develop our vaccine, now in Phase 2 clinical trials, and for which we anticipate starting Phase 3 efficacy trials around the world in the coming weeks."

DISCLAIMER: FN Media Group LLC (FNM), which owns and operates Financialnewsmedia.com and MarketNewsUpdates.com, is a third- party publisher and news dissemination service provider, which disseminates electronic information through multiple online media channels.FNM is NOT affiliated in any manner with any company mentioned herein. FNM and its affiliated companies are a news dissemination solutions provider and are NOT a registered broker/dealer/analyst/adviser, holds no investment licenses and may NOT sell, offer to sell or offer to buy any security.FNM's market updates, news alerts and corporate profiles are NOT a solicitation or recommendation to buy, sell or hold securities. The material in this release is intended to be strictly informational and is NEVER to be construed or interpreted as research material.All readers are strongly urged to perform research and due diligence on their own and consult a licensed financial professional before considering any level of investing in stocks. All material included herein is republished content and details which were previously disseminated by the companies mentioned in this release.FNM is not liable for any investment decisions by its readers or subscribers. Investors are cautioned that they may lose all or a portion of their investment when investing in stocks. For current services performed FNM was compensated twenty five hundred dollars for news coverage of current press release issued by NanoViricides, Inc. by a non-affiliated third party.FNM HOLDS NO SHARES OF ANY COMPANY NAMED IN THIS RELEASE.

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Nanomedicine Seen As A Promising Approach For Diagnosis and Treatment Against COVID - PRNewswire

Heres how healthcare industry is evolving with technology – AppleMagazine

From applying leeches in medieval times to the development of nanotechnology in the modern world, we have come a long way. Lets take a look at this guide and follow the new healthcare industry trends about technology. For more info, you can check out metime.com.

In the medical industry, tech is associated with multiple radical changes. People can handle the COVID situation better because of the presence of tech in the healthcare setup. Here are some of the most widely recognized and used tech changes in the Health sector:

With telemedicine, you can receive medical attention via various communication modes, including audio or video calls. You can now connect to the best healthcare professional from any part of the globe.

Doctors had to face various problems due to the manual record-keeping process. There was always a threat of damaging or losing data. This problem is solved with the help of EHRs. Moreover, its comparatively easier to transfer the details of a patient to another doctor.

Many applications are aided by an AI, capable of learning and developing on their own. The AI uses information uploaded in the database.

What are the benefits of technology in the healthcare sector?

The entry of tech in medicine can be considered a blessing in disguise for many doctors and patients. Some of them are mentioned below:

The beginning of telemedicine was marked by the accessibility of healthcare services for all the people. Imagine you live in a remote area, and you see a rash on your arm. All you need to do is click a picture and upload it along with your application symptoms. Then it will direct you to a proper doctor.

It helps people detect problems at an early stage so that doctors could stop the prognosis of a particular disease. It can also prove to be handy to figure out the possibility of new conditions and ways to tackle them.

People always fear that machines would replace them, and they could end up losing their jobs. Instead, you would require people that can guide you through the maze of systems and complex machinery. This situation, in turn, means more people would get hired.

Once you begin to bring a change in the world, youre bound to face some challenges. They help you to find loopholes in your products or services so that you can improve them. The developers are always vigilant regarding the ability of their device or software to function at full capacity.

A brief list of challenges are posing a threat to the advancement of the medical sector:

A persons medical records consist of much detailed personal information. If it falls into the wrong hands, it can cause unimaginable damage to the person. Moreover, some places are still using old tech, making it easier for hackers to get their hands on the precious data.

In most medical setups, you might find physicians that are experienced and accomplished in their fields. However, this experience comes from years of practice. So, at their given age, learning a complex skill can cause hindrance to the workflow. Even if they can get the hang of a tech piece, it might get replaced with another version.

Many hospitals and small scale clinics find it hard to keep up with the changes as new technology is quite expensive. Moreover, theres a chance that your vendor drastically stops making that particular product without any warnings. So, if that system stops working, then your entire workflow and structure might come crumbling down.

Any medical facility is filled with many machines that are used by different departments. With the EHR innovation, all of you need to do is scan the barcode, and every record would be digitalized. However, as astounding it sounds, it can be a bit more chaotic. Due to the lack of structure and organization of the data, bringing forth the information could be problematic.

As you know, people would keep searching for new ways to make your lives more comfortable and hassle-free. Its safe to say that youre now familiar with the techs involvement in medicine. Heres what more you can expect in the coming years.

The touch of reality makes augmented reality different from virtual reality. The ability to make speedy availability of data has paved the way for AR in the medicine market. It can be beneficial for students learning to be surgeons or physicians. As compared to a dummy or real body, you can better understand human anatomy with an AR.

Telehealth can be of aid for numerous purposes, but you still need to visit a hospital for surgery. Robots in operation theatre can cut down the chances of human error to a great extent. This improvement, in turn, decreases the pain and speeds up the recovery process. Moreover, it can also shield the doctors from all the tremendous amount of stress they bear.

The presence of nanotechnology inside someones body could be overwhelming to some people. However, what people fail to understand is that it can help us better understand complex issues like cancer or allergies. The primary role of nanomedicine is to detect, treat, and even restrain various diseases from spreading.

It has vast potential, from printing artificial limbs to creating blood vessels. Individual doctors are trying to perfect the art of printing actual human skin, which includes blood vessels. It can be a boon for people suffering from third-degree burns. Soon, you can also expect the pharmaceutical companies to print FDA approved 3-D drugs.

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Heres how healthcare industry is evolving with technology - AppleMagazine

Development of safe liver sinusoid coating agents to increase the efficacy of gene therapy – Science Codex

5pm on June 26, 2020 - Kawasaki/Japan: The Innovation Center of NanoMedicine (iCONM), the National Institute for Quantum Science and Technology (QST), and the University of Tokyo jointly announced that a reagent for the selective and safe coating of the liver sinusoidal walls to control the clearance of gene therapy drugs was successfully developed. The contents of this research will be published in Science Advances by the American Association for the Advancement of Science (AAAS) at 2:00 pm on June 26, east coast of the United States (Japan standard time: 3:00 am on 27th): A. Dirisala, S. Uchida, K. Toh, J. Li, S. Osawa, T. A. Tockary, X. Liu, S. Abbasi, K. Hayashi, Y. Mochida, S. Fukushima, H. Kinoh, K. Osada, Kazunori Kataoka, "Transient stealth coating of liver sinusoidal wall by anchoring two-armed PEG for retargeting nanomedicines".

Recently, gene therapies have been successively approved in Europe, US, and Japan, and are expected to provide novel therapeutic options for cancer, chronic diseases, acquired and inherited genetic disorders. Whilst this is promising, in reality, when gene therapy drugs are systemically administered to living organisms, they are rapidly eliminated and metabolized in the liver, thus impeding the delivery of a sufficient amount to the target organs and raising the toxicity concerns. This elimination by the liver is caused by the adsorption of the gene therapy drugs to the vascular wall of the liver sinusoid, which is an intrahepatic capillary. To overcome this issue, we conceived to selectively coat the liver sinusoidal wall using polyethylene glycol (PEG). However, a long-term coating may impair the normal physiological functions of the liver, and therefore the coating should be transient. In addition, coating needs to be selective for liver sinusoids, as coating the blood vessels throughout the body would not only cause adverse effects but also decrease the delivery amount of gene therapy drugs to target organs. Towards this end, we have developed a coating agent with two-armed PEG conjugated to positively charged oligolysine, which demonstrated the selective coating on the liver sinusoidal wall, the first-of-its-kind strategy in the world. Interestingly, the coating with two-armed PEG was excreted into bile within 6 hours after binding to sinusoidal walls, while the coating with single chain of linear PEG bound to oligolysine persisted in the walls for a long time. In this way, the precise molecular design was necessary to achieve a transient coating.

This coating was subsequently applied to boost the delivery efficacy of gene therapy drugs. Adeno-associated virus (AAV) is widely used for viral gene therapy drugs, and its serotype 8 (AAV8) targets myocardium and skeletal muscles. When AAV8 was administered after prior coating of two-armed PEG to the liver sinusoidal wall, the transfer of AAV8 to the liver was suppressed, and as a result, the gene transfer efficiency into the myocardium and skeletal muscles was improved by 2 to 4 times. This approach is promising for the treatment of muscular dystrophy. In addition, we expanded the use of our strategy to virus-free gene delivery systems, which allows more economically attractive and safe gene therapy. We have been working on non-viral gene therapy for malignant tumors using plasmid DNA-equipped smart nanomachine for over 10 years. When the coating agent was used for this system, the adsorption of nanomachines to the sinusoidal wall was suppressed, resulting in an approximately 10-fold improvement in DNA transfer efficiency to colon cancer. As described above, we have succeeded in boosting the activity of gene therapy drugs while ensuring safety by using the coating agent developed this time.

The above findings are summarized as follows:

- The coating agent with two-armed PEG selectively coated the liver sinusoid wall for several hours and was then excreted in the bile.

- The coating agent with single chain of linear PEG is not excreted in bile and coated the liver sinusoidal wall for more than 9 hours, which raises a safety concern.

- The coating agent with two-armed PEG had selectivity for the liver sinusoid wall, without coating the blood vessels in the connective tissues.

- The coating agent improved the gene transfer efficacy to the myocardium and skeletal muscles using the AAV vector by 2 to 4 times, and the gene transfer efficiency to colorectal cancer using DNA-loaded smart nanomachines by 10 times.

- As a result, our approach is expected to allow for improving the effect of gene therapy drugs and reducing their dose needed to obtain therapeutic outcome, which will lead to the reduction of medical cost and adverse event opportunities.

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Development of safe liver sinusoid coating agents to increase the efficacy of gene therapy - Science Codex

Nanomedicine Market Segmentation By Qualitative And Quantitative Research Incorporating Impact Of Economic And Non-Economic Aspects By 2027 – Reports…

The report on the Global Nanomedicine Market provides a panoramic view of the current developments and progresses within the Nanomedicine market. The report further analyzes the impact of the novel COVID-19 pandemic on the Nanomedicine market and provides an accurate insight into the current and future market fluctuations. Factors likely to influence the growth of the market, current trends, opportunities, restraining factors, and business landscape are discussed in-depth in the market study.

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The major players profiled in the global Nanomedicine market report include:

Arrowhead Pharmaceuticals Inc. AMAG Pharmaceuticals, Bio-Gate AG, Celgene Corporation, and Johnson & Johnson.

Market Segment by Regions:

Product Outlook (Revenue, USD Billion; 2017-2027)

Drug Delivery System Outlook (Revenue, USD Billion; 2017-2027)

Application Outlook (Revenue, USD Billion; 2017-2027)

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Healthcare Nanotechnology (Nanomedicine) Market : Updates, Future Growth, Industry Analysis And Comprehensive Study On Key Players To 2020 2028 -…

Healthcare Nanotechnology (Nanomedicine) Market is analyzed with industry experts in mind to maximize return on investment by providing clear information needed for informed business decisions. This research will help both established and new entrants to identify and analyze market needs, market size and competition. It explains the supply and demand situation, the competitive scenario, and the challenges for market growth, market opportunities and the threats faced by key players.

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Sanofi SA, Pfizer Inc., Celgene Corporation, Luminex Corporation, and Taiwan Liposome Company Ltd.

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By Application (Drug Delivery, Biomaterials, Active Implants, Diagnostic Imaging, Tissue Regeneration), By Disease (Cardiovascular Diseases, Oncological Diseases, Neurological Diseases, Orthopedic Diseases, Infectious Diseases and Other Diseases)

Healthcare Nanotechnology (Nanomedicine)

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Healthcare Nanotechnology (Nanomedicine) Market : Updates, Future Growth, Industry Analysis And Comprehensive Study On Key Players To 2020 2028 -...

Global Healthcare Nanotechnology (Nanomedicine) Market 2020 with (Covid-19) Impact Analysis: Business Outlook, Future Growth and Regional Forecasts…

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The report presents insightful analyses of the market and has a comprehensive understanding of the global Healthcare Nanotechnology (Nanomedicine) market industry analysis and forecast 2020-2025 and its commercial landscape. Critical aspects such as impacting factors and competitive landscape are showcased with the help of vital resources, such as charts, tables, and infographics. The complete value chain and downstream and upstream essentials are scrutinized in this report. It additionally seriously explored the global Healthcare Nanotechnology (Nanomedicine) market development pattern based on regional order. Marketing strategies and different channels have been listed here.

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NOTE: Our analysts monitoring the situation across the globe explains that the market will generate remunerative prospects for producers post COVID-19 crisis. The report aims to provide an additional illustration of the latest scenario, economic slowdown, and COVID-19 impact on the overall industry.

Key companies profiled in the market report are Amgen, Merck & Co, UCB, Teva Pharmaceuticals, Sanofi, Abbott, Stryker, Celgene, Roche, Biogen, SmitH& Nephew, Takeda, Gilead Sciences, Endo International, Leadiant Biosciences, Johnson & Johnson, Pfizer, Ipsen, Kyowa Hakko Kirin, 3M Company, and more in terms of company basic information, product introduction, application, specification, production, revenue, price and gross margin (2015-2020), etc.

Differentiation of the market based on types of product: Nanomedicine, Nano Medical Devices, Nano Diagnosis, Other

Differentiation of the market based on types of its application: Anticancer, CNS Product, Anti-infective, Other

Geographically, this report studies the top producers and consumers in these key regions: North America (United States, Canada and Mexico), Europe (Germany, France, United Kingdom, Russia and Italy), Asia-Pacific (China, Japan, Korea, India, Southeast Asia and Australia), South America (Brazil, Argentina), Middle East & Africa (Saudi Arabia, UAE, Egypt and South Africa). Here each geographic segment of the Healthcare Nanotechnology (Nanomedicine) market has been independently investigated along with pricing, distribution, and demand data for geographic market.

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Global Healthcare Nanotechnology (Nanomedicine) Market 2020 with (Covid-19) Impact Analysis: Business Outlook, Future Growth and Regional Forecasts...

Nanomedicine: Nanotechnology, Biology and Medicine …

The mission of Nanomedicine: Nanotechnology, Biology, and Medicine (Nanomedicine: NBM) is to promote the emerging interdisciplinary field of nanomedicine.

Nanomedicine: NBM is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.

Nanomedicine: NBM journal publishes articles on artificial cells, regenerative medicine, gene therapy, infectious disease, nanotechnology, nanobiotechnology, nanomedicine, stem cell and tissue engineering.

Sub-categories include synthesis, bioavailability, and biodistribution of nanomedicines; delivery, pharmacodynamics, and pharmacokinetics of nanomedicines; imaging; diagnostics; improved therapeutics; innovative biomaterials; interactions of nanomaterials with cells, tissues, and living organisms; public health; toxicology; theranostics; point of care monitoring; nutrition; nanomedical devices; prosthetics; biomimetics; and bioinformatics.

Article formats include Rapid Communications, Original Articles, Reviews, Perspectives, Technical and Commercialization Notes, and Letters to the Editor. We invite authors to submit original manuscripts in these categories.

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Nanomedicine: Nanotechnology, Biology and Medicine ...

Ex-ERC head loses paper over image duplication – Times Higher Education (THE)

A scientific paper co-authored by the former president of the European Research Council has been retracted after duplicated images were detected in the research.

In anannouncementon 26 June, the journalScience Advancessaid that it had retracted a paper published in April on what appeared to be a potentially game-changing method of delivering diabetes drugs orally, rather than through injections.

The paper,titledMolecular targeting of FATP4 transporter for oral delivery of therapeutic peptide, seemed to offerhopethat drugs for other diseases, such as rheumatoid arthritis and other autoimmune diseases, could eventually be given as a pill.

The results, which showed how mice were able to absorb the drug effectively in their stomachs, appeared to clear the way for clinical trials on humans, the studys corresponding author Haifa Shen, professor of nanomedicine at the Houston Methodist Research Institute, told theMedical Xpresswebsite in April.

Among the papers authors all of whom were associated with the Houston institute at the time of publication was Mauro Ferrari, who was head of the European Research Council for three months earlier this year before quitting in April over what he saw as the European Unions response to the coronavirus pandemic.

Science Advances, the only open-access journal in theSciencefamily of journals, says that it retracted the paper after readers identified duplicated image regions in multiple figure panels.

Alerted to these concerns, the corresponding authors institution performed a review of the supporting data and research records and determined that the research was not performed according to expected standards and was not reliable, it says.

Therefore, we wish to retract this research article promptly, it continues, adding that it apologise[s] that these errors were not discovered before the manuscript was published.

The journal said that all the authors had agreed that the paper should be retracted, except one its lead author Zhenhua Hu, who did not respond to his co-authors communications.

Times Higher Education contacted Professor Shen, who conducted the review of readers concerns, for comment.

Following Professor Ferraris resignation from the ERC, senior officials said that they had asked him to resign over a litany of failings that predated the pandemic, including spending too much time in the US and a complete lack of appreciation for the raison dtre of the ERC, namely bottom-up research suggested by academics, rather than top-down efforts dictated from above.

jack.grove@timeshighereducation.com

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Ex-ERC head loses paper over image duplication - Times Higher Education (THE)

Securing Medical Technology in the Age of COVID-19 – Infosecurity Magazine

Consider the miracle of a pacemaker that promotes heartbeat regularity or an insulin pump that ensures a diabetics pancreatic function both are devices operated by a distant network. Now, imagine if those networks were to fail.Particularly in the age of COVID-19, technology experts are feeling the pressure to develop new strategies to tackle healthcare challenges. Cyber threats in the field of medical technology range from hacking of IoT medical devices, such as insulin pumps and pacemakers, to the PHI of cardiac arrest patients being locked by ransomware attackers, thus preventing timely treatment of patients in critical condition due to heart attack.

While thousands of patients utilize such medical devices, the security of these systems lies with the networks remotely powering the device. Moreover, nanomedicine or the use of nantotechnology for healthcare purposes such as eradication of cancer cells also relies on such distant networks. Like any computer network, SCADA systems face risks from a variety of cyber-attacks.

Recently, Dr. Gregory Carpenter, a Cyber Epidemiologist at KnowledgeBridge International Inc., has revealed his teams investigation results, including the discovery that 23 of the 25 bio-nano carrier networks tested were vulnerable to basic DDoS attacks, as well as other legacy threats such as outdated and unpatched systems exposed to zero-day attacks.

The operational nature of SCADA especially in healthcare remains highly collaborative, with medical staff sharing data amongst themselves as well as hospital IT teams sharing information with cloud brokers and providers. Indeed, as more medical organizations migrate to the cloud, such data sharing coupled with the lack of visibility inherent to the cloud environment poses many risks.

As the attack surface increases l with both medical IoT and PHIs exposure to the cloud, hospitals and medical device providers could benefit from ensuring that patient information is encrypted and their cloud providers have secure defenses in place against denial of service attacks.

In the area of cloud security, healthcare organizations should e bear in mind that while their cloud service providers control the physical security of the servers in their data centers, as cloud customers, the organizations themselves hold responsibility for encrypting data in transit. Therefore, all data whether PHI or related to the operations of medical technology should remain top priority for in-transit security.

In-transit encryption best practices involve the key elements of defining data protection requirements, implementing secure certificate and stored key management, automating data leak detection and authenticating network communications via IPSec or TLS protocols. Such steps to enforcement will help assure that data moving between the cloud provider and healthcare entity endpoint remains secure.

A helpful starting point might entail configuring load balancers to only interact with HTTPS traffic in order to promote encrypted movement of data between the host organization and cloud service provider. Another solution to in-transit security lies in the use of VPN between the cloud provider and healthcare customer. Additionally, both provider and customer must maintain cognizance surrounding faults in availability, in terms of impact to quality of care as well as implications regarding the potential underlying context of such events.

In particular, phishing campaigns have often worked in parallel to larger-scale attacks such as DDoS, in an attempt to infiltrate the target network while security teams focus on the availability-based incident. Therefore, healthcare senior management and IT personnel who observe compromise attempts via network intrusion detection data can help safeguard against a breach by warning all employees to remain vigilant regarding potential phishing emails.

As email-based attacks have especially targeted the healthcare industry amidst the recent COVID-19 crisis, medical professionals and their patients stand to gain the most from hospital management and practitioners learning how to avoid such correlated threats.

To this effect, security awareness training provides an optimal defense against the possibility for data compromise by human error. With fewer physicians and hospital administrators falling victim to scareware and other malicious email-based activity, the attack vector shrinks for cyber-criminals looking to capitalize on the panic over the current global pandemic.

Furthermore, network administrators in the healthcare space can do their part by tightly monitoring infrastructure for any penetration attempt. A place to begin might be examining signs of botnet activity and other availability-based attacks with phishing attempts that occur within a similar timeframe of around 24 hours or fewer. As soon as a security team detects a compromise, all associated medical devices must be immediately remotely deactivated.

Perhaps most importantly, providers of biotechnology as well as hospital services must maintain transparency with all customers and patients regarding any suspected or successful breaches. After all, the individuals receiving treatment in these instances face the highest risk, as any successful attacker holds the power to not only access PHI, but potentially also to hack into a medical device on which a human life might depend.

Sarah Katz is an author working in information security at NASA. Since graduating from UC Berkeley, she has published various pieces in research and science fiction, primarily surrounding the intersection of medicine and technology. Most recently, she has founded Cysec Health, a nonprofit group of cybersecurity volunteers supporting women's health organizations amid the COVID-19 pandemic.

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Securing Medical Technology in the Age of COVID-19 - Infosecurity Magazine

Global Nanobots Market 2020 with COVID-19 After Effects Analysis by Emerging Trends, Industry Demand, Growth, Key Players – Cole of Duty

Researchstore.biz has added the latest up-to-date research entitled Global Nanobots Market 2020 by Manufacturers, Regions, Type and Application, Forecast to 2025 its huge collection of research reports. The report comprises a thorough study of the current trends leading to this vertical trend in various regions. The report has included important details related to global Nanobots market share, market size, applications, statistics, and sales. It offers details about market definition, market drivers, market restraints, market segmentation with respect to product usage and geographical conditions, key developments taking place in the market, competitor analysis, and the research methodology.

Market Analysis Coverage:

Furthermore, this global Nanobots market report provides details of new recent developments, trade regulations, import-export analysis, production analysis, value chain optimization, market share, the impact of domestic and localized market players, analyses opportunities in terms of emerging revenue, changes in market regulations, strategic market growth analysis, market size, category market growths, product approvals, product launches, geographic expansions, technological innovations in the market. Additional, data points such as consumption volumes, production sites, and volumes, price trend analysis, cost of raw materials, downstream and upstream value chain analysis are some of the major pointers used to forecast the market scenario for individual countries for 2020 to 2025 time period.

NOTE: This report takes into account the current and future impacts of COVID-19 on this industry and offers you an in-dept analysis of Nanobots market.

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Industry Size:

The global Nanobots market size is a key component of strategic marketing planning. The report provides an understanding of the size of the target industry, allowing you to fully analyze opportunities and accurately plan your approach and your investments. An accurate understanding of market size will provide you with a number of significant advantages that will help you keep your business grow over time.

This report focused and concentrates on these companies including: Xidex Corp, Ginkgo Bioworks, Zymergen Inc, Synthace Limited, Advanced Nano Products Co Limited, Advanced Diamond Technologies

Market segment by product type, split into Microbivore Nanorobots, Respirocyte Nanorobots, Clottocyte Nanorobots, Cellular Repair Nanorobots, , along with their consumption (sales), market share and growth rate

Market segment by application, split into Nano Medicine, Biomedical, Mechanical, Other applications, along with their consumption (sales), market share and growth rate

This report focuses on the global Nanobots market status, future forecast, growth opportunity, key market, and key players. The study objectives are to present the development in North America (United States, Canada and Mexico), Europe (Germany, France, UK, Russia and Italy), Asia-Pacific (China, Japan, Korea, India and Southeast Asia), South America (Brazil, Argentina, etc.), Middle East& Africa (Saudi Arabia, Egypt, Nigeria and South Africa).

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Total Chapters In This Market Report Are:

Chapter 1: Overview of global Nanobots market

Chapter 2: Global growth trends

Chapter 3: Market share by key players

Chapter 4: Breakdown data by type and application

Chapter 5: North America market status by countries, type, manufacturers and downstream industry

Chapter 6: Europe Market status by countries, type, manufacturers and downstream industry

Chapter 7: Asia Pacific market status by countries, type, manufacturers and downstream industry

Chapter 8: South America market status by countries, type, manufacturers and downstream industry

Chapter 9: the Middle East and Africa market status by countries, type, manufacturers and downstream industry

Chapter 10: Market driving factor analysis

Chapter 11: Market competition status by major manufacturers

Chapter 12: International players profiles

Chapter 13: Market Forecast 2020-2025

Chapter 14: Analysts Viewpoints/Conclusions

Chapter 15: Appendix

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About Us

Researchstore.biz is a fully dedicated global market research agency providing thorough quantitative and qualitative analysis of extensive market research.Our corporate is identified by recognition and enthusiasm for what it offers, which unites its staff across the world.We are desired market researchers proving a reliable source of extensive market analysis on which readers can rely on. Our research team consist of some of the best market researchers, sector and analysis executives in the nation, because of which Researchstore.biz is considered as one of the most vigorous market research enterprises. Researchstore.biz finds perfect solutions according to the requirements of research with considerations of content and methods. Unique and out of the box technologies, techniques and solutions are implemented all through the research reports.

Contact UsMark StoneHead of Business DevelopmentPhone: +1-201-465-4211Email: [emailprotected]Web: http://www.researchstore.biz

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Global Nanobots Market 2020 with COVID-19 After Effects Analysis by Emerging Trends, Industry Demand, Growth, Key Players - Cole of Duty

Nanobiotix Announces Positive First Results From Phase I Expansion in Locally Advanced Head and Neck Cancer at ASCO 2020 – Press Release – Digital…

PARIS & CAMBRIDGE, Mass.--(Business Wire)--Regulatory News:

NANOBIOTIX (Paris:NANO)(Euronext: NANO - ISIN: FR0011341205 the Company), a clinical-stage nanomedicine company pioneering new approaches to the treatment of cancer, today announced new data from the expansion part of its phase I trial, evaluating the potential of first-in-class NBTXR3 activated by radiation therapy to improve treatment outcomes for elderly patients with locally advanced head and neck cancer ineligible for chemotherapy or intolerant to cetuximab. The data were published as part of the virtual scientific program at the 2020 annual meeting of the American Society for Clinical Oncology (ASCO).

Study 102: A phase I trial of hafnium oxide nanoparticles activated by radiotherapy in cisplatin-ineligible locally advanced HNSCC patients

Authors: Christophe Le Tourneau, Valentin Calugaru, Edith Borcoman, Victor Moreno, Emiliano Calvo, Xavier Liem, Sebastien Salas, Bernard Doger, Olivier Choussy, Maria Lesnik, Xavier Mirabel, Nathalie Badois, Samar Krhili, Josefin Blomkvist, Nicolas Fakhry, Stphanie Wong-Hee-Kam, Caroline Hoffmann.

J Clin Oncol 38: 2020 (suppl; abstr 6573). DOI: 10.1200/JCO.2020.38.15_suppl.6573.

Abstract Number: 6573

Study Design

After reporting promising early signs of activity from the dose escalation part of its phase I trial evaluating the safety and feasibility of NBTXR3 activated by radiation therapy in elderly patients with locally advanced head and neck squamous cell carcinoma (HNSCC), the Company launched an expansion cohort to confirm results and observed trends with a larger population treated at the recommended dose. This part of the study is expected to recruit a total of 44 evaluable patients. To date, 40 patients have been recruited, 30 of whom are evaluable for efficacy and are included in the data presented at ASCO 2020.

Topline Results

As previously announced, in the dose escalation part of the study NBTXR3 activated by radiation therapy was safe and well tolerated. The recommended phase 2 dose (RP2D) was determined to be 22% of baseline tumor volume. Among 16 evaluable patients, injected lesion complete response rate was 56% and overall objective response rate was 69%.

Regarding the new, expansion part data, analysis of 40 patients dosed showed that NBTXR3 activated by radiation therapy remains safe and well tolerated. In terms of efficacy, for the 30 evaluable patients, investigators observed, at a median time of 5 months after NBTXR3 injection, an overall objective response rate of 83% and an overall complete response rate of 43% and objective response rate of the primary tumor (target lesion) of 83% with a complete response rate of the primary tumor of 60%. The safety profile was consistent with the dose escalation part and the efficacy data improved (i.e. an increase in overall objective response rate from 69% in the dose escalation part to 83% in the dose expansion part).

In the safety population (all treated patients, N=40), three serious adverse events (SAEs) related to NBTXR3 were observed (0.7% of all AEs), comprising one case each of: Grade 4 tumor hemorrhage also related to radiotherapy, Grade 3 mucosal inflammation and Grade 2 swollen tongue also related to the injection procedure. Two SAEs related to the injection procedure were reported (0.5% of all AEs), comprising: two cases of swollen tongue, of which one was Grade 2 and also related to NBTXR3, and one was Grade 4. The radiotherapy-associated safety profile was as expected with the most frequently occurring AEs being stomatitis and skin injury. Three deaths due to AEs related to radiotherapy and other causes were observed. Four other patients died of non-oncologic or non-toxicity-related reasons.

Next Steps in Head and Neck Cancer

The expansion part of the phase I trial will continue to recruit until reaching 44 evaluable patients. In parallel, subject to the FDAs pending review, the Company intends to globally launch a pivotal phase III trial. In the planned phase III trial, a futility analysis is expected 18 months after the first patient is randomized, and an interim analysis of progression-free survival (PFS) is expected at 24-30 months.

NBTXR3 for the treatment of locally advanced HNSCC patients who are not eligible for platinum-based chemotherapy received Fast Track designation from the FDA in February 2020. Fast Track designation is a process designed to facilitate the development and accelerate the review of drugs for serious conditions that have the potential to address unmet medical needs. The purpose is to expedite the availability of new treatment options for patients.

About NBTXR3

NBTXR3 is a first-in-class product designed to destroy tumors through physical cell death when activated by radiotherapy. NBTXR3 has a high degree of biocompatibility, requires one single administration before the first radiotherapy treatment session, and has the ability to fit into current worldwide radiation therapy standards of care. The physical mode of action of NBTXR3 makes it applicable across solid tumors.

NBTXR3 is being evaluated in locally advanced head and neck squamous cell carcinoma (HNSCC) of the oral cavity or oropharynx in elderly patients unable to receive chemotherapy or cetuximab with limited therapeutic options. Promising results have been observed in the phase I trial regarding local control. In the United States, the Company has started the regulatory process to commence a phase III clinical trial in locally advanced head and neck cancers.

Nanobiotix is also running an Immuno-Oncology development program. The Company has launched a Phase I clinical trial of NBTXR3 activated by radiotherapy in combination with anti-PD-1 checkpoint inhibitors in locoregional recurrent (LRR) or recurrent and metastatic (R/M) HNSCC amenable to re-irradiation of the HN and lung or liver metastases (mets) from any primary cancer eligible for anti-PD-1 therapy.

Other ongoing NBTXR3 trials are treating patients with hepatocellular carcinoma (HCC) or liver metastases, locally advanced or unresectable rectal cancer in combination with chemotherapy, head and neck cancer in combination with concurrent chemotherapy, and pancreatic cancer. The Company has a broad, comprehensive clinical research collaboration with The University of Texas MD Anderson Cancer Center (initially expected to support 9 new clinical trials in the United States) to evaluate NBTXR3 across several cancer types.

About NANOBIOTIX: http://www.nanobiotix.com

Incorporated in 2003, Nanobiotix is a leading, clinical-stage nanomedicine company pioneering new approaches to significantly change patient outcomes by bringing nanophysics to the heart of the cell.

The Nanobiotix philosophy is rooted in designing pioneering, physical-based approaches to bring highly effective and generalized solutions to address unmet medical needs and challenges.

Nanobiotixs first-in-class, proprietary lead technology, NBTXR3, aims to expand radiotherapy benefits for millions of cancer patients. Nanobiotixs Immuno-Oncology program has the potential to bring a new dimension to cancer immunotherapies.

Nanobiotix is listed on the regulated market of Euronext in Paris (Euronext: NANO / ISIN: FR0011341205; Bloomberg: NANO: FP). The Companys headquarters are in Paris, France, with a US affiliate in Cambridge, MA, and European affiliates in France, Spain and Germany.

Disclaimer

This press release contains certain forward-looking statements concerning Nanobiotix and its business, including its prospects and product candidate development. Such forward-looking statements are based on assumptions that Nanobiotix considers to be reasonable. However, there can be no assurance that the estimates contained in such forward-looking statements will be verified, which estimates are subject to numerous risks including the risks set forth in the universal registration document of Nanobiotix approved by the French Financial Markets Authority (Autorit des Marchs Financiers) under number R.20-010 on May 12, 2020 (a copy of which is available on http://www.nanobiotix.com) and to the development of economic conditions, financial markets and the markets in which Nanobiotix operates. The forward-looking statements contained in this press release are also subject to risks not yet known to Nanobiotix or not currently considered material by Nanobiotix. The occurrence of all or part of such risks could cause actual results, financial conditions, performance or achievements of Nanobiotix to be materially different from such forward-looking statements.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200529005528/en/

Nanobiotix Communications Department Brandon Owens +1 (617) 852-4835contact@nanobiotix.com

Investor Relations Department Ricky Bhajun +33 (0)1 79 97 29 99investors@nanobiotix.com

Media Relations France TBWA Corporate Pauline Richaud + 33 (0) 437 47 36 42Pauline.richaud@tbwa-corporate.com

US RooneyPartners Marion Janic +1 (212) 223-4017mjanic@rooneyco.com

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Nanobiotix Announces Positive First Results From Phase I Expansion in Locally Advanced Head and Neck Cancer at ASCO 2020 - Press Release - Digital...

Global Healthcare Nanotechnology Market :Growth and Changes Influencing the Industry 2020-2026 – News Distinct

The research report on Healthcare Nanotechnology Market provides comprehensive analysis on market status and development pattern, including types, applications, rising technology and region. Healthcare Nanotechnology Market report covers the present and past market scenarios, market development patterns, and is likely to proceed with a continuing development over the forecast period. The report covers all information on the global and regional markets including historic and future trends for market demand, size, trading, supply, competitors, and prices as well as global predominant vendors information.

The Outlook Of Global Healthcare Nanotechnology Market:

AmgenTeva PharmaceuticalsAbbottUCBRocheCelgeneSanofiMerck & CoBiogenStrykerGilead SciencesPfizer3M CompanyJohnson & JohnsonSmith & NephewLeadiant BiosciencesKyowa Hakko KirinShireIpsenEndo International

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Market Segment by Regions, regional analysis covers

North America (United States, Canada and Mexico)

Europe (Germany, France, UK, Russia and Italy)

Asia-Pacific (China, Japan, Korea, India and Southeast Asia)

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Middle East and Africa (Saudi Arabia, UAE, Egypt, Nigeria and South Africa)

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NanomedicineNano Medical DevicesNano DiagnosisOther

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AnticancerCNS ProductAnti-infectiveOther

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The competitive landscape of the Healthcare Nanotechnology Market is discussed in the report, including the market share and new orders market share by company. The report profiles some of the leading players in the global market for the purpose of an in-depth study of the challenges faced by the industry as well as the growth opportunities in the market. The report also discusses the strategies implemented by the key companies to maintain their hold on the industry. The business overview and financial overview of each of the companies have been analyzed.

This report provide wide-ranging analysis of the impact of these advancements on the markets future growth, wide-ranging analysis of these extensions on the markets future growth. The research report studies the market in a detailed manner by explaining the key facets of the market that are foreseeable to have a countable stimulus on its developing extrapolations over the forecast period.

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What will the market size in the forecast period?

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Who are the key players, vendors, and sellers of Healthcare Nanotechnology Market?

What are the influencing factors of the global market?

Table of Contents:

Global Healthcare Nanotechnology Market Research Report

Chapter 1-Healthcare Nanotechnology Market Overview

Chapter 2 Global Economic Impact on Industry

Chapter 3 Global Market Competition by Manufacturers

Chapter 4 Global Production, Revenue (Value) by Region

Chapter 5 Global Supply (Production), Consumption, Export, Import by Regions

Chapter 6 Global Production, Revenue (Value), Price Trend by Type

Chapter 7 Global Market Analysis by Application

Chapter 8 Manufacturing Cost Analysis

.CONTINUED FOR TOC

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Global Healthcare Nanotechnology Market :Growth and Changes Influencing the Industry 2020-2026 - News Distinct

Nanobots Market Growth by Top Companies, Trends by Types and Application, Forecast to 2026| Xidex Corp, Zymergen Inc, Synthace Limited, Ginkgo…

LOS ANGELES, United States:QY Research has recently published a report, titled Global Nanobots Market Research Report 2020-2026.The research report provides an in-depth explanation of the various factors that are likely to drive the market. It discusses the future of the market by studying the historical details. Analysts have studied the ever-changing market dynamics to evaluate their impact on the overall market. In addition, the Nanobots report also discusses the segments present in the market. Primary and secondary research methodologies have been used to provide the readers with an accurate and precise understanding of the overall Nanobots market. Analysts have also given readers an unbiased opinion about the direction companies will take during the forecast period.

The research report also includes the global Nanobots market figures that provide historical data as well as estimated figures. It gives a clear picture of the growth rate of the market during the forecast period. The Nanobots report aims to give the readers quantifiable data that is collected from verified data. The report attempts to answer all the difficult questions such as market sizes and company strategies.

Download Full PDF Sample Copy ofNanobots Report with TOC, figure and tables: https://www.qyresearch.com/sample-form/form/1738855/impact-of-covid-19-outbreak-on-nanobots-global-and-japan-market

The vendor landscape and competitive scenarios of the global Nanobots market are broadly analyzed to help market players gain competitive advantage over their competitors. Readers are provided with detailed analysis of important competitive trends of the global Nanobots market. Market players can use the analysis to prepare themselves for any future challenges well in advance. They will also be able to identify opportunities to attain a position of strength in the global Nanobots market. Furthermore, the analysis will help them to effectively channelize their strategies, strengths, and resources to gain maximum advantage in the global Nanobots market.

Key Players Mentioned in the Global Nanobots Market Research Report: Xidex Corp, Zymergen Inc, Synthace Limited, Ginkgo Bioworks, Advanced Diamond Technologies, Advanced Nano Products Co Limited

Global Nanobots Market Segmentation by Product: Microbivore Nanorobots, Respirocyte Nanorobots, Clottocyte Nanorobots, Cellular Repair Nanorobots

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The report comes out as an accurate and highly detailed resource for gaining significant insights into the growth of different product and application segments of the global Nanobots market. Each segment covered in the report is exhaustively researched about on the basis of market share, growth potential, drivers, and other crucial factors. The segmental analysis provided in the report will help market players to know when and where to invest in the global Nanobots market. Moreover, it will help them to identify key growth pockets of the global Nanobots market.

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Table of Content

1 Study Coverage1.1 Nanobots Product Introduction1.2 Market Segments1.3 Key Nanobots Manufacturers Covered: Ranking by Revenue1.4 Market by Type1.4.1 Global Nanobots Market Size Growth Rate by Type1.4.2 Microbivore Nanorobots1.4.3 Respirocyte Nanorobots1.4.4 Clottocyte Nanorobots1.4.5 Cellular Repair Nanorobots1.5 Market by Application1.5.1 Global Nanobots Market Size Growth Rate by Application1.5.2 Nano Medicine1.5.3 Biomedical1.5.4 Mechanical1.5.5 Other applications1.6 Coronavirus Disease 2019 (Covid-19): Nanobots Industry Impact1.6.1 How the Covid-19 is Affecting the Nanobots Industry1.6.1.1 Nanobots Business Impact Assessment Covid-191.6.1.2 Supply Chain Challenges1.6.1.3 COVID-19s Impact On Crude Oil and Refined Products1.6.2 Market Trends and Nanobots Potential Opportunities in the COVID-19 Landscape1.6.3 Measures / Proposal against Covid-191.6.3.1 Government Measures to Combat Covid-19 Impact1.6.3.2 Proposal for Nanobots Players to Combat Covid-19 Impact1.7 Study Objectives1.8 Years Considered

2 Executive Summary2.1 Global Nanobots Market Size Estimates and Forecasts2.1.1 Global Nanobots Revenue 2015-20262.1.2 Global Nanobots Sales 2015-20262.2 Nanobots Market Size by Region: 2020 Versus 20262.3 Nanobots Historical Market Size by Region (2021-2026)2.3.1 Global Nanobots Retrospective Market Scenario in Sales by Region: 2015-20202.3.2 Global Nanobots Retrospective Market Scenario in Revenue by Region: 2015-20202.4 Nanobots Market Estimates and Projections by Region (2021-2026)2.4.1 Global Nanobots Sales Forecast by Region (2021-2026)2.4.2 Global Nanobots Revenue Forecast by Region (2021-2026)

3 Global Nanobots Competitor Landscape by Players3.1 Global Top Nanobots Sales by Manufacturers3.1.1 Global Nanobots Sales by Manufacturers (2015-2020)3.1.2 Global Nanobots Sales Market Share by Manufacturers (2015-2020)3.2 Global Nanobots Manufacturers by Revenue3.2.1 Global Nanobots Revenue by Manufacturers (2015-2020)3.2.2 Global Nanobots Revenue Share by Manufacturers (2015-2020)3.2.3 Global Nanobots Market Concentration Ratio (CR5 and HHI) (2015-2020)3.2.4 Global Top 10 and Top 5 Companies by Nanobots Revenue in 20193.2.5 Global Nanobots Market Share by Company Type (Tier 1, Tier 2 and Tier 3)3.3 Global Nanobots Price by Manufacturers3.4 Global Nanobots Manufacturing Base Distribution, Product Types3.4.1 Nanobots Manufacturers Manufacturing Base Distribution, Headquarters3.4.2 Manufacturers Nanobots Product Type3.4.3 Date of International Manufacturers Enter into Nanobots Market3.5 Manufacturers Mergers & Acquisitions, Expansion Plans

4 Breakdown Data by Type (2015-2026)4.1 Global Nanobots Market Size by Type (2015-2020)4.1.1 Global Nanobots Sales by Type (2015-2020)4.1.2 Global Nanobots Revenue by Type (2015-2020)4.1.3 Nanobots Average Selling Price (ASP) by Type (2015-2026)4.2 Global Nanobots Market Size Forecast by Type (2021-2026)4.2.1 Global Nanobots Sales Forecast by Type (2021-2026)4.2.2 Global Nanobots Revenue Forecast by Type (2021-2026)4.2.3 Nanobots Average Selling Price (ASP) Forecast by Type (2021-2026)4.3 Global Nanobots Market Share by Price Tier (2015-2020): Low-End, Mid-Range and High-End

5 Breakdown Data by Application (2015-2026)5.1 Global Nanobots Market Size by Application (2015-2020)5.1.1 Global Nanobots Sales by Application (2015-2020)5.1.2 Global Nanobots Revenue by Application (2015-2020)5.1.3 Nanobots Price by Application (2015-2020)5.2 Nanobots Market Size Forecast by Application (2021-2026)5.2.1 Global Nanobots Sales Forecast by Application (2021-2026)5.2.2 Global Nanobots Revenue Forecast by Application (2021-2026)5.2.3 Global Nanobots Price Forecast by Application (2021-2026)

6 China by Players, Type and Application6.1 China Nanobots Market Size YoY Growth 2015-20266.1.1 China Nanobots Sales YoY Growth 2015-20266.1.2 China Nanobots Revenue YoY Growth 2015-20266.1.3 China Nanobots Market Share in Global Market 2015-20266.2 China Nanobots Market Size by Players (International and Local Players)6.2.1 China Top Nanobots Players by Sales (2015-2020)6.2.2 China Top Nanobots Players by Revenue (2015-2020)6.3 China Nanobots Historic Market Review by Type (2015-2020)6.3.1 China Nanobots Sales Market Share by Type (2015-2020)6.3.2 China Nanobots Revenue Market Share by Type (2015-2020)6.3.3 China Nanobots Price by Type (2015-2020)6.4 China Nanobots Market Estimates and Forecasts by Type (2021-2026)6.4.1 China Nanobots Sales Forecast by Type (2021-2026)6.4.2 China Nanobots Revenue Forecast by Type (2021-2026)6.4.3 China Nanobots Price Forecast by Type (2021-2026)6.5 China Nanobots Historic Market Review by Application (2015-2020)6.5.1 China Nanobots Sales Market Share by Application (2015-2020)6.5.2 China Nanobots Revenue Market Share by Application (2015-2020)6.5.3 China Nanobots Price by Application (2015-2020)6.6 China Nanobots Market Estimates and Forecasts by Application (2021-2026)6.6.1 China Nanobots Sales Forecast by Application (2021-2026)6.6.2 China Nanobots Revenue Forecast by Application (2021-2026)6.6.3 China Nanobots Price Forecast by Application (2021-2026)

7 North America7.1 North America Nanobots Market Size YoY Growth 2015-20267.2 North America Nanobots Market Facts & Figures by Country7.2.1 North America Nanobots Sales by Country (2015-2020)7.2.2 North America Nanobots Revenue by Country (2015-2020)7.2.3 U.S.7.2.4 Canada

8 Europe8.1 Europe Nanobots Market Size YoY Growth 2015-20268.2 Europe Nanobots Market Facts & Figures by Country8.2.1 Europe Nanobots Sales by Country8.2.2 Europe Nanobots Revenue by Country8.2.3 Germany8.2.4 France8.2.5 U.K.8.2.6 Italy8.2.7 Russia

9 Asia Pacific9.1 Asia Pacific Nanobots Market Size YoY Growth 2015-20269.2 Asia Pacific Nanobots Market Facts & Figures by Country9.2.1 Asia Pacific Nanobots Sales by Region (2015-2020)9.2.2 Asia Pacific Nanobots Revenue by Region9.2.3 China9.2.4 Japan9.2.5 South Korea9.2.6 India9.2.7 Australia9.2.8 Taiwan9.2.9 Indonesia9.2.10 Thailand9.2.11 Malaysia9.2.12 Philippines9.2.13 Vietnam

10 Latin America10.1 Latin America Nanobots Market Size YoY Growth 2015-202610.2 Latin America Nanobots Market Facts & Figures by Country10.2.1 Latin America Nanobots Sales by Country10.2.2 Latin America Nanobots Revenue by Country10.2.3 Mexico10.2.4 Brazil10.2.5 Argentina

11 Middle East and Africa11.1 Middle East and Africa Nanobots Market Size YoY Growth 2015-202611.2 Middle East and Africa Nanobots Market Facts & Figures by Country11.2.1 Middle East and Africa Nanobots Sales by Country11.2.2 Middle East and Africa Nanobots Revenue by Country11.2.3 Turkey11.2.4 Saudi Arabia11.2.5 U.A.E

12 Company Profiles12.1 Xidex Corp12.1.1 Xidex Corp Corporation Information12.1.2 Xidex Corp Description, Business Overview and Total Revenue12.1.3 Xidex Corp Sales, Revenue and Gross Margin (2015-2020)12.1.4 Xidex Corp Nanobots Products Offered12.1.5 Xidex Corp Recent Development12.2 Zymergen Inc12.2.1 Zymergen Inc Corporation Information12.2.2 Zymergen Inc Description, Business Overview and Total Revenue12.2.3 Zymergen Inc Sales, Revenue and Gross Margin (2015-2020)12.2.4 Zymergen Inc Nanobots Products Offered12.2.5 Zymergen Inc Recent Development12.3 Synthace Limited12.3.1 Synthace Limited Corporation Information12.3.2 Synthace Limited Description, Business Overview and Total Revenue12.3.3 Synthace Limited Sales, Revenue and Gross Margin (2015-2020)12.3.4 Synthace Limited Nanobots Products Offered12.3.5 Synthace Limited Recent Development12.4 Ginkgo Bioworks12.4.1 Ginkgo Bioworks Corporation Information12.4.2 Ginkgo Bioworks Description, Business Overview and Total Revenue12.4.3 Ginkgo Bioworks Sales, Revenue and Gross Margin (2015-2020)12.4.4 Ginkgo Bioworks Nanobots Products Offered12.4.5 Ginkgo Bioworks Recent Development12.5 Advanced Diamond Technologies12.5.1 Advanced Diamond Technologies Corporation Information12.5.2 Advanced Diamond Technologies Description, Business Overview and Total Revenue12.5.3 Advanced Diamond Technologies Sales, Revenue and Gross Margin (2015-2020)12.5.4 Advanced Diamond Technologies Nanobots Products Offered12.5.5 Advanced Diamond Technologies Recent Development12.6 Advanced Nano Products Co Limited12.6.1 Advanced Nano Products Co Limited Corporation Information12.6.2 Advanced Nano Products Co Limited Description, Business Overview and Total Revenue12.6.3 Advanced Nano Products Co Limited Sales, Revenue and Gross Margin (2015-2020)12.6.4 Advanced Nano Products Co Limited Nanobots Products Offered12.6.5 Advanced Nano Products Co Limited Recent Development12.11 Xidex Corp12.11.1 Xidex Corp Corporation Information12.11.2 Xidex Corp Description, Business Overview and Total Revenue12.11.3 Xidex Corp Sales, Revenue and Gross Margin (2015-2020)12.11.4 Xidex Corp Nanobots Products Offered12.11.5 Xidex Corp Recent Development

13 Market Opportunities, Challenges, Risks and Influences Factors Analysis13.1 Market Opportunities and Drivers13.2 Market Challenges13.3 Market Risks/Restraints13.4 Porters Five Forces Analysis13.5 Primary Interviews with Key Nanobots Players (Opinion Leaders)

14 Value Chain and Sales Channels Analysis14.1 Value Chain Analysis14.2 Nanobots Customers14.3 Sales Channels Analysis14.3.1 Sales Channels14.3.2 Distributors

15 Research Findings and Conclusion

16 Appendix16.1 Research Methodology16.1.1 Methodology/Research Approach16.1.2 Data Source16.2 Author Details

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Nanobots Market Growth by Top Companies, Trends by Types and Application, Forecast to 2026| Xidex Corp, Zymergen Inc, Synthace Limited, Ginkgo...

NanoViricides is Developing Drugs Against SARS-CoV-2 with an Integrated Approach to Combat COVID-19, as Reported at The LD 500 Virtual Conference -…

SHELTON, CT / ACCESSWIRE / September 4, 2020 / NanoViricides, Inc. (NYSE American: NNVC) (the "Company") a global leader in the development of highly effective antiviral therapies based on a novel nanomedicines platform, today reported on the Presentation by Anil R. Diwan, Ph.D., its President and Executive Chairman, at the LD 500 investor conference yesterday, Thursday, September 3rd at 11:20 AM EDT.

Dr. Diwan presented the Company's rapid progress in developing a drug to attack the SARS-CoV-2 virus that causes COVID-19 spectrum of diseases.

He summarized the Company's progress since embarking into this endeavor with very limited resources since about January, 2020, and boot-strapping on its past work against coronaviruses. Dr. Diwan stated that the Company is close to declaring a clinical candidate for treating patients infected with SARS-CoV-2. The Company has previously reported that its development candidates have shown to be effective against multiple coronaviruses in the Company's own BSL2 Virology Lab, and have also shown to be highly effective in an animal study to combat infection by a related coronavirus that uses the same ACE2 receptor as does SARS-CoV-2.

Dr. Diwan stated that this broad-spectrum effectiveness against coronaviruses provides scientific reasoning that even as a field coronavirus strain mutates, our drug candidates would continue to remain effective, unlike antibodies and vaccines.

In addition, our current development candidates against COVID-19 have also been shown to be extremely safe in animal studies. Their effectiveness in cell culture and animal models has led us to believe that they are worthy of human clinical development.

Subsequently, the Company has completed CMC ("Chemistry, Manufacture, and Controls") studies that would be required for an IND ("Investigational New Drug) application to the U.S. FDA. The Company is also in the process of drafting sections of an IND for COVID-19 drug candidate. The Company is currently conducting studies to finalize its clinical candidate.

Dr. Diwan further stated the Company's intent of developing an integrated approach to combat SARS-CoV-2 that could potentially result in a cure for the virus. The virus lifecycle is a convolution of two parts: (a) re-infection of a host cell by external virus (after primary infection from outside the host body), and (b) replication (i.e. production of new virus particles) in infected cells and egress of the newly produced virus particles to feed back into the (a) re-infection cycle, completing the loop.

Dr. Diwan explained that if both parts of the virus lifecycle are blocked, then a virus infection would be cured, except in the case of latent viruses.

A nanoviricide® is uniquely capable of accomplishing this task of integrated attack against both the re-infection and replication mechanisms, as the Company has previously stated. The nanoviricide is already designed to block the re-infection cycle part. In addition, it can carry in its "belly", a payload that can block the replication cycle part.

NanoViricides has accelerated its anti-coronavirus program to develop a "second generation" nanoviricide against coronaviruses that is designed to block both re-infection and replication cycles, in addition to the current development of the "first generation" anti-coronavirus drug intended to block the re-infection cycle part. The Company accelerated these efforts due to both the severity of the pandemic, and the difficulty of curing the SARS-CoV-2 infection as exemplified by several recent unsuccessful or partially successful clinical studies.

In particular, the Company has successfully encapsulated remdesivir inside its current development drug candidates. The resulting drug, which is expected to be superior to remdesivir alone, as well as many other drugs, is already in pre-clinical testing, Dr. Diwan disclosed.

Remdesivir inhibits replication cycle by blocking the RNA polymerase activity essential for virus genome duplication. It is highly effective in cell culture studies against many viruses. However, its success in reducing viral load and pathology has been limited in human clinical studies. This is probably substantially due to the extensive metabolism that the drug is subjected to as soon as it enters the bloodstream.

Encapsulation into a nanoviricide is anticipated to protect remdesivir from this extensive metabolism and thus improve its clinical effect profile. Additionally, the nanoviricide itself is expected to block the re-infection cycle part of the virus lifecycle. Thus the Company believes that this novel integrated nanomedicine approach could produce a highly effective drug against coronaviruses, and against SARS-CoV-2 in particular, possibly on the way to a cure.

The Company develops its class of drugs, that we call nanoviricides®, using a platform technology. This approach enables rapid development of new drugs against a number of different viruses. A nanoviricide is a "biomimetic" - it is designed to "look like" the cell surface to the virus. The nanoviricide® technology enables direct attacks at multiple points on a virus particle. It is believed that such attacks would lead to the virus particle becoming ineffective at infecting cells. Antibodies in contrast attack a virus particle at only a maximum of two attachment points per antibody.

Because of the worldwide urgency of the pandemic caused by the SARS-CoV-2 virus, we have focused all our efforts recently on taking a drug against SARS-CoV-2 into human clinical trials for treatment of patients with COVID-19. An effective drug could potentially allow full-fledged opening of normal activities, including schools, businesses, and economies all over the world.

Soon after it files an IND for a COVID-19 drug candidate, the Company intends to re-engage its NV-HHV-101 shingles drug candidate clinical trials program towards IND filing. The Company has put the shingles program on hold due to perceived difficulties in conducting proposed shingles clinical trials during the COVID-19 pandemic. The Company is near finalizing the selection of clinical trial sites and finalizing clinical trial protocols for the shingles IND filing.

The NV-HHV-101 drug candidate is expected to open up a billion dollar market for the shingles treatment space, and also lead to further development of drugs against other herpesviruses such as HSV-1 that causes "cold sores" and HSV-2 that causes genital herpes. The multiple indications enabled by the HerpeCide program drug candidates may potentially address a several billion dollar marketspace.

For additional information about NanoViricides, please visit the company's website at http://www.nanoviricides.com .

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. Our lead drug candidate is NV-HHV-101 with its first indication as dermal topical cream for the treatment of shingles rash. The Company is in the process of completing an IND application to the US FDA for this drug candidate. The Company cannot project an exact date for filing an IND because of its dependence on a number of external collaborators and consultants, the effects of recent COVID-19 restrictions, and re-prioritization for COVID-19 drug development work.

The Company is also developing drugs against a number of viral diseases including oral and genital Herpes, viral diseases of the eye including EKC and herpes keratitis, H1N1 swine flu, H5N1 bird flu, seasonal Influenza, HIV, Hepatitis C, Rabies, Dengue fever, and Ebola virus, among others. NanoViricides' platform technology and programs are based on the TheraCour® nanomedicine technology of TheraCour, which TheraCour licenses from AllExcel. NanoViricides holds a worldwide exclusive perpetual license to this technology for several drugs with specific targeting mechanisms in perpetuity for the treatment of the following human viral diseases: Human Immunodeficiency Virus (HIV/AIDS), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Rabies, Herpes Simplex Virus (HSV-1 and HSV-2), Varicella-Zoster Virus (VZV), Influenza and Asian Bird Flu Virus, Dengue viruses, Japanese Encephalitis virus, West Nile Virus and Ebola/Marburg viruses. The Company has executed a Memorandum of Understanding with TheraCour that provides a limited license for research and development for drugs against human coronaviruses. The Company intends to obtain a full license and has begun the process for the same. The Company's technology is based on broad, exclusive, sub-licensable, field licenses to drugs developed in these areas from TheraCour Pharma, Inc. The Company's business model is based on licensing technology from TheraCour Pharma Inc. for specific application verticals of specific viruses, as established at its foundation in 2005.

This press release contains forward-looking statements that reflect the Company's current expectation regarding future events. Actual events could differ materially and substantially from those projected herein and depend on a number of factors. Certain statements in this release, and other written or oral statements made by NanoViricides, Inc. are "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. You should not place undue reliance on forward-looking statements since they involve known and unknown risks, uncertainties and other factors which are, in some cases, beyond the Company's control and which could, and likely will, materially affect actual results, levels of activity, performance or achievements. The Company assumes no obligation to publicly update or revise these forward-looking statements for any reason, or to update the reasons actual results could differ materially from those anticipated in these forward-looking statements, even if new information becomes available in the future. Important factors that could cause actual results to differ materially from the company's expectations include, but are not limited to, those factors that are disclosed under the heading "Risk Factors" and elsewhere in documents filed by the company from time to time with the United States Securities and Exchange Commission and other regulatory authorities. Although it is not possible to predict or identify all such factors, they may include the following: demonstration and proof of principle in preclinical trials that a nanoviricide is safe and effective; successful development of our product candidates; our ability to seek and obtain regulatory approvals, including with respect to the indications we are seeking; the successful commercialization of our product candidates; and market acceptance of our products. FDA refers to US Food and Drug Administration. IND application refers to "Investigational New Drug" application. CMC refers to "Chemistry, Manufacture, and Controls".

Contact: NanoViricides, Inc. info@nanoviricides.com

Public Relations Contact: MJ Clyburn TraDigital IR clyburn@tradigitalir.com

SOURCE: NanoViricides, Inc.

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NanoViricides is Developing Drugs Against SARS-CoV-2 with an Integrated Approach to Combat COVID-19, as Reported at The LD 500 Virtual Conference -...

Brigham and Womens researchers unveil cutting-edge innovation in virtual showcase – Boston Herald

Researchers from Brigham and Womens Hospital unveiled an array of cutting-edge medical technology in a Thursday virtual showcase that included a bedside teddy bear powered by artificial intelligence and a nasal spray that can prevent the spread of viruses.

The Discover Brigham event united doctors and scientists from all corners of the medical community to share the latest research and development of ideas and products that can shape the health care industry.

One such development is a nasal spray that can prevent the transmission of respiratory viruses by capturing and killing the inhaled aerosols in the nasal cavity.

In addition to containing the virus, the components of the formulation are also able to deactivate the virus within a few minutes of capture, said John Joseph, BWH postdoctoral fellow in the Center for Nanomedicine.

The pocket-sized spray coats the nasal cavity for up to four hours without irritation or sensory impairment, and can be used as a barrier when masks arent feasible such as while eating and drinking, Joseph said during Thursdays virtual demo. Researchers expect to test the spray against COVID-19 soon.

The spray is drug free, and will be cleared via mucus and expelled from the body through digestion three to four hours after use.

Our strategy has been designed in such a way that it can be easily integrated into daily life, Joseph said, adding that the product would play an especially important role in the context of the current and future pandemics.

On the softer side of the presentations sat Briggie, a plush teddy bear toy with the power of artificial intelligence that can ask patients about their pain level and respond to their requests.

Briggie has activating buttons, LED lights, a microcomputer, a microphone and a smart speaker to interact with patients, but it isnt like other smart technology.

It doesnt work like Alexa or Siri, it doesnt listen all the time, said Dr. Samir Tulebaev, Brigham associate physician.

Instead, Briggie is activated every hour, or whenever you need it, to ask about four key things pain, positioning, personal comfort and toileting.

Hello, my name is Briggie. I am an artificial intelligence nursing assistant. I will be asking about your pain every hour. I will send a text message to your nurse if you need any help, Briggie said during the demo.

When the patient is discharged from the hospital, they get to take the Briggie plush toy home with them.

Other innovations presented Thursday included artificial intelligence solutions to maintain stable vital signs during Cesarean delivery, an injection molded prototype N95 respirator for health care workers and many others.

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Brigham and Womens researchers unveil cutting-edge innovation in virtual showcase - Boston Herald

Impact of Covid-19 on Nanorobots Market Current Scenario, Bruker, Jeol, Thermo Fisher, Ginkgo Bioworks, Oxford Instruments, etc. – 3rd Watch News

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Impact of Covid-19 on Nanorobots Market Current Scenario, Bruker, Jeol, Thermo Fisher, Ginkgo Bioworks, Oxford Instruments, etc. - 3rd Watch News

Transient stealth coating of liver sinusoidal wall by anchoring two-armed PEG for retargeting nanomedicines – Science Advances

Abstract

A major critical issue in systemically administered nanomedicines is nonspecific clearance by the liver sinusoidal endothelium, causing a substantial decrease in the delivery efficiency of nanomedicines into the target tissues. Here, we addressed this issue by in situ stealth coating of liver sinusoids using linear or two-armed poly(ethylene glycol) (PEG)conjugated oligo(l-lysine) (OligoLys). PEG-OligoLys selectively attached to liver sinusoids for PEG coating, leaving the endothelium of other tissues uncoated and, thus, accessible to the nanomedicines. Furthermore, OligoLys having a two-armed PEG configuration was ultimately cleared from sinusoidal walls to the bile, while OligoLys with linear PEG persisted in the sinusoidal walls, possibly causing prolonged disturbance of liver physiological functions. Such transient and selective stealth coating of liver sinusoids by two-arm-PEG-OligoLys was effective in preventing the sinusoidal clearance of nonviral and viral gene vectors, representatives of synthetic and nature-derived nanomedicines, respectively, thereby boosting their gene transfection efficiency in the target tissues.

Nanomedicines have been widely studied for the efficient delivery of therapeutic and diagnostic agents into target tissues (16). However, nanomedicines are exposed to several clearance mechanisms, such as reticuloendothelial system (RES) uptake, after their systemic administration (79). Among these mechanisms, liver sinusoidal endothelial cells (LSECs) express numerous types of scavenger receptors for capturing a variety of nanomedicines and have high endocytic activity to clear them actively from the blood circulation (1012). The targets of LSEC-mediated clearance include both synthetic and nature-derived nanomedicines, such as viral gene vectors (13, 14), limiting their delivery efficiency to the target tissues.

To address this issue of LSEC-mediated clearance, the stealth coating of nanomedicines, e.g., by poly(ethylene glycol) (PEG), which allows nanomedicines to persist in the blood circulation for hours to days, has been widely attempted (1518). However, depending on the formulation of the nanomedicine and its drug contents, it is often difficult to obtain sufficient stealth coating to completely inhibit the clearance mechanisms without compromising nanomedicine functionality (1922). Thus, a combination of other strategies is required. The modulation of host-tissue clearance mechanisms is a promising option. For this purpose, previous studies have attempted to saturate the availability of clearing sites, e.g., by preinjecting scavenger receptor ligands, such as fucoidan (23), polyinosinic acid (poly-I) (24), and dextran sulfate (DS) (25), or decoy nanoparticles, such as polymer-albumin nanoparticles (26) and cationic liposomes (27). However, this strategy has two major problems. First, agents used for receptor saturation inhibit only specific mechanisms of sinusoidal clearance, depending on the receptors or clearance sites that they target, despite the fact that the liver sinusoid has diverse clearance pathways. Even a single nanomedicine can be recognized by several receptors (12, 28, 29), such that the simultaneous inhibition of various clearance mechanisms is preferred. Second, the receptor saturation strategy often raises safety concerns, including inflammatory responses induced by fucoidan (30) or poly-I (31) and anticoagulation associated with the administration of DS (32).

To circumvent these issues, herein we propose transient and selective stealth coating of liver sinusoidal endothelium, using precisely designed PEGylated oligocation (Fig. 1). In contrast to the previous strategy of receptor saturation, PEG coating of liver sinusoidal endothelium would be effective for the simultaneous inhibition of various clearance mechanisms. The coating should be transient and selective to the liver sinusoid to avoid toxicity concerns. This was achieved by using oligo(l-lysine) (OligoLys) conjugated with two-armed PEG at its carboxyl end (two-arm-PEG-OligoLys) for anchoring PEG to liver sinusoidal walls. The PEGylation of OligoLys allowed us to avoid the nonspecific attachment of OligoLys to the extra-liver endothelium, presumably via the steric repulsion of PEG, with preserved binding capability to liver sinusoidal endothelium, which may have high binding affinity to oligocations because of the abundance of heparan sulfate proteoglycans and scavenger receptors (11, 33, 34). The clearance behavior of the PEGylated OligoLys was successfully controlled by optimizing the PEG configuration, with two-arm-PEG-OligoLys showing transient PEG coating to the liver sinusoidal endothelium, followed by gradual biliary clearance, while the OligoLys conjugated with one-armed (linear) PEG (one-arm-PEG-OligoLys) bound to the sinusoidal endothelium persistently. Subsequently, transient and selective stealth coating of liver sinusoids by two-arm-PEG-OligoLys was found to be effective in preventing the sinusoidal clearance of nonviral and viral gene vectors, providing an increased gene transfection efficiency in their target tissues via their relocation from the liver sinusoid to the tissues.

(A) OligoLys with 20 Lys units conjugated with two linear chains of 40-kDa PEG at its carboxyl end (two-arm-PEG-OligoLys). (B) Schematic illustration of in situ stealth coating of liver sinusoidal wall. Two-arm-PEG-OligoLys selectively attaches to the sinusoidal wall to prevent the attachment of nanomedicines, such as polyplex micelle (PM) and adeno-associated virus (AAV), to the wall via stealth property of PEG. Two-arm-PEG-OligoLys is gradually cleared to the bile to avoid prolonged disturbance of liver sinusoid functions.

Short OligoLys with approximately 20 Lys units was used, as the shortening of the oligo-polycation is an effective strategy to circumvent toxicity concerns (35, 36). OligoLys was PEGylated in two different methods, using either one- or two-armed PEG. A single linear chain of 80-kDa PEG or double linear chains of 40-kDa PEG were conjugated to OligoLys at the proximal -NH2 terminus of PEG by forming a stable covalent amide bond to the distal carboxyl end of OligoLys (Fig. 2A). We selected the PEGylated OligoLys samples to have the same total Mw (weight-average molecular weight) of PEG in each molecule, i.e., 80 kDa. Total PEG Mw was set to 80 kDa for avoiding renal clearance of PEGylated OligoLys (37), which may influence its sinusoidal coating behavior. Note that each molecule of two-arm-PEG-OligoLys has two 40-kDa PEG strands, meaning that total Mw of PEG per OligoLys strand in the molecule is set at 80 kDa, and this is the same PEG Mw ratio to OligoLys as that in each of the one-arm-PEG-OligoLys molecule with a single strand of 80-kDa PEG. In this way, we can faithfully evaluate the effect of PEG configuration (linear versus two-arm branched) without an influence of total Mw of PEG fraction in each PEGylated OligoLys molecule. These PEGylated OligoLys formulations were labeled with a single molecule of Alexa Fluor 594 at the OligoLys main chain -NH2 group for the real-time fluorescence observation of their pharmacokinetic behaviors in living mice using intravital confocal laser scanning microscopy (IVCLSM).

(A) Chemical structures of one-arm-PEG-OligoLys (top, left), two-arm-PEG-OligoLys (top, right) with or without Alexa594 labeling (bottom). (B to D) Alexa594-labeled OligoLys with or without PEGylation was intravenously injected. Five minutes or 1 hour after the injection, earlobe dermis was observed using IVCLSM. (B) One-arm-PEG-OligoLys. (C) Two-arm-PEG-OligoLys. (D) Non-PEGylated OligoLys. Arrowheads, capillary walls. Two-way arrows, capillary lumen.

When observing the earlobe dermis, a representative connective tissue, after intravenous injection of one- and two-arm-PEG-OligoLys, the fluorescence intensity of the blood vessel walls was comparable with that of the lumen (Fig. 2, B and C), indicating no PEGylated OligoLys attachment to the vessel walls of the earlobe. On the contrary, non-PEGylated OligoLys with approximately 28 Lys units was aligned to the vessel walls of the earlobe as early as 5 min after injection (Fig. 2D). Thus, the attachment of OligoLys to the vessel walls of a connective tissue was successfully avoided by PEGylation of OligoLys, presumably due to stealth properties of PEG.

In sharp contrast, both one- and two-arm-PEG-OligoLys were attached to the vessel walls of the liver sinusoid within 5 min after injection (Fig. 3, A and B). Quantitative analysis revealed a much higher fluorescence intensity of the sinusoidal wall compared with the lumen (Fig. 3, C and D). This observation indicates the successful PEG coating of the liver sinusoidal wall after the injection of one- and two-arm-PEG-OligoLys. These PEGylated OligoLys formulations attached more efficiently to the blood vessel walls of the liver compared with those of the connective tissue (Fig. 2, B and C). Such selective binding of one- and two-arm-PEG-OligoLys to the liver sinusoidal wall may be attributed to the abundancy of anionic proteoglycans, such as heparan sulfate proteoglycans, present on the sinusoidal extracellular matrix, which can capture oligocations (33, 34), as well as to the high expression levels of scavenger receptors, which recognize cationic macromolecules, on sinusoidal cells (11).

(A to D) IVCLSM images after injection of Alexa594-labeled one-arm-PEG-OligoLys (A) and two-arm-PEG-OligoLys (B). Green, autofluorescence of liver parenchyma. Red, one- and two-arm-PEG-OligoLys. Presumable regions of bile canaliculi are encircled with white dotted lines. Intensity profiles of Alexa594 in the white arrows in (A) and (B) are shown in (C) and (D), respectively. (C) One-arm-PEG-OligoLys. (D) Two-arm-PEG-OligoLys. (E) Bile ducts were visualized using 5-carboxyfluorescein (CF, green). Then, Alexa594-labeled two-arm-PEG-OligoLys (magenta) was injected for observation 7 hours later. Colocalization of these two colors is observed as white or cyan (encircled by yellow dotted lines). (F) Blood circulation profiles of PEG without OligoLys, and one- and two-arm-PEG-OligoLys. n = 4. Data are shown as means SEM.

The two-arm-PEG-OligoLys fluorescence signal at the sinusoidal wall gradually decreased and became almost undetectable at 6 hours or later after injection (Fig. 3, B and D), whereas one-arm-PEG-OligoLys remained localized to the sinusoidal wall even at 9 hours after injection, with a minimal decrease in the fluorescence intensity of the sinusoidal wall during the observation period (Fig. 3, A and C). Closer observation revealed that two-arm-PEG-OligoLys was progressively accumulated to the space between the hepatocytes (encircled with dotted lines in Fig. 3B) at 3 hours or later after injection, whereas one-arm-PEG-OligoLys exhibited an almost undetectable accumulation to that space even at 9 hours after injection. On the basis of its anatomical position, the space may correspond to the bile canaliculi, which collect the bile from hepatocytes for clearance through the bile ducts. To clarify this point, a fluorescent bile tracer, 5-carboxyfluorescein (CF), was injected 5 min before two-arm-PEG-OligoLys injection. The position of two-arm-PEG-OligoLys accumulation at 7 hours after injection was colocalized with that of CF, as observed in the white or cyan pixels in Fig. 3E, which resulted from the merging of green (CF) and magenta pixels (two-arm-PEG-OligoLys). These observations indicate the gradual biliary clearance of two-arm-PEG-OligoLys.

The clearance profile of one- and two-arm-PEG-OligoLys was additionally evaluated by observing their persistence in the blood circulation. While these two groups showed comparable blood circulation profile within 1 hour after injection, obvious differences were observed at 1 hour or later after injection (Fig. 3F); the blood concentration of two-arm-PEG-OligoLys gradually decreased, while that of one-arm-PEG-OligoLys remained almost constant. The blood concentrations of one- and two-arm-PEG-OligoLys fit the two-compartment model with high R2 values, in which the polymers were administered into the central compartment and subsequently distributed into a tissue compartment (fig. S1 and table S1). These two formulations showed a comparable distribution phase half-life of around 15 min, with a comparable distribution rate constant (k12). This is consistent with the observation that both formulations similarly showed rapid binding to hepatic sinusoids. On the other hand, the elimination phase half-life of one-arm-PEG-OligoLys (13.3 hours) was much longer than that of two-arm-PEG-OligoLys (5.7 hours), which may reflect the different clearance behaviors of these two groups. The blood circulation profile of PEG without OligoLys conjugation fits the one-compartment model with high R2 values and presented a long half-life (19.8 hours). Without binding to vessel walls, this formulation may lack a distribution phase.

To obtain further mechanistic insights into the different behaviors between one- and two-arm-PEG-OligoLys, these two formulations were coinjected into mice for IVCLSM observation of their distribution in the hepatic sinusoids after labeling one-arm-PEG-OligoLys with Alexa647 (fig. S2, red) and two-arm-PEG-OligoLys with Alexa594 (green). Both formulations showed comparable levels of liver sinusoidal accumulation at 5 min to 1 hour after injection (Fig. 4 and movie S1). This observation suggests that the binding affinity of these formulations to the sinusoids is comparable. In sharp contrast, fluorescence from two-arm-PEG-OligoLys in the sinusoidal wall became weak, especially 6 hours or later after injection, presumably through biliary clearance, while a strong fluorescence signal from one-arm-PEG-OligoLys was consistently observed in the wall. Eventually, the sinusoidal walls in the images gradually became red (one-arm-PEG-OligoLys), with green (two-arm-PEG-OligoLys) appearing in the presumable location of the bile canaliculi 6 hours or later after injection. This observation is consistent with that after the single injection of each formulation, with two-arm-PEG-OligoLys still gradually cleared in the presence of one-arm-PEG-OligoLys. Thus, one-arm-PEG-OligoLys may preserve the liver functionality of biliary clearance but failed to be cleared under these conditions.

Alexa647-labeled one-arm-PEG-OligoLys (red) and Alexa594-labeled two-arm-PEG-OligoLys (green) were coinjected from the tail vein. (A) IVCLSM imaging of the liver. Presumable regions of bile canaliculi are encircled with white dotted lines. (B to D) Intensity profiles of Alexa594 and Alexa647 in the white arrows shown in (A). (B) 0.5 min, (C) 5 min, and (D) 6 hours after injection.

Toward safe usage of two-arm-PEG-OligoLys, it is important to estimate its clearance rate. For this purpose, blood clearance profile of two-arm-PEG-OligoLys was observed under its continuous intravenous infusion. In this experiment, bolus intravenous injection of two-arm-PEG-OligoLys was performed at a dose of 1250 g per mouse, which is the same as that used throughout this study. Subsequently, two-arm-PEG-OligoLys was infused at the rate reduced in a stepwise manner, to find the rate that allows the blood level of two-arm-PEG-OligoLys to be constant. Under such condition, the infusion rate of two-arm-PEG-OligoLys would be balanced with its clearance rate. The blood level of two-arm-PEG-OligoLys was constant under the infusion rate of 1200 g/hour per mouse and gradually decreased under the rate of 630 g/hour per mouse (fig. S3). This result suggests that the clearance rate of two-arm-PEG-OligoLys was approximately 1200 g/hour per mouse. This clearance may occur mainly through the biliary pathway, as two-arm-PEG-OligoLys with molecular weight over 80 kDa is unlikely to be cleared through the renal pathway. Two-arm-PEG-OligoLys accumulation to the bile canaliculi was observed in intravital observation of the liver 3 hours or later after the injection (Fig. 3B). It is also worthy to note that the biliary clearance rate of two-arm-PEG-OligoLys (1200 g/hour per mouse = 240 pmol/min per mouse) is comparable with that of cationic drugs (100 to 1000 pmol/min per mouse), as reported previously (38).

We then checked hemolysis and change in major biomarkers related to liver and kidney functions to estimate potential acute toxicity of injected polymers. Two-arm-PEG-OligoLys, as well as one-arm-PEG-OligoLys, showed no ex vivo hemolytic activity (fig. S4) and no detectable changes in plasma levels of a general tissue damage marker [lactate dehydrogenase (LDH)], liver damage markers [aspartate aminotransaminase (AST) and alanine aminotransferase (ALT)], and kidney function markers [blood urea nitrogen (BUN) and creatinine (Cre)] after in vivo administration (table S2). On the other hand, non-PEGylated OligoLys induced a substantial level of hemolysis activity ex vivo and LDH release in vivo.

Together, the above results demonstrate that the clearance behavior of the PEGylated OligoLys was successfully controlled by fine-tuning of PEG configuration. PEGylated OligoLys formulations used for the transient stealth coating of liver sinusoidal wall should simultaneously meet the following two requisites: (i) sufficient and selective stealth coating of the liver sinusoidal wall for retargeting nanomedicines and (ii) ensured clearance from the sinusoidal wall for avoiding chronic disturbance of physiological functions due to accumulation of PEG-OligoLys in the body. As shown in Figs. 2 and 3, both one- and two-arm-PEG-OligoLys attached to the sinusoidal walls selectively, meeting requisite (i). Worth noting is that two-arm-PEG-OligoLys was able to be cleared from the sinusoidal wall to the bile in several hours, while one-arm-PEG-OligoLys persisted on the wall even after 9 hours of the observation period. This result indicates that one-arm-PEG-OligoLys does not satisfy requisite (ii), which may induce safety concerns of chronic accumulation toxicity. Thus, we selected only two-arm-PEG-OligoLys for further examination devoted to evaluate redirecting efficacy of nanomedicines, demonstrating the enhanced gene expression of polyplex micelle (PM) and adeno-associated virus (AAV) in target tissues as described in the following sections.

To evaluate the feasibility of the sinusoidal PEG coating strategy, we first selected PM loading plasmid DNA (pDNA) as a model nanomedicine (39, 40). PM was prepared by mixing pDNA with one-arm-PEG-poly(l-lysine) (PLys) block copolymers with a PEG Mw of 12 kDa and a PLys polymerization degree of 44, installed with thiol moieties in 50% of the lysine residues for environment-responsive cross-linking between the cationic segments of the block copolymers. The PM was composed of a PEG shell and a core containing condensed pDNA. Disulfide cross-linking in the core stabilizes PM in extracellular environments and is selectively cleaved in intracellular reductive environments for pDNA release. According to our previous report, despite the stealth and stabilized PM formulation, a large fraction of the PM was cleared from the blood circulation within 1 hour after systemic injection, with only 23% of the dose remaining in the blood at 1 hour after injection (40). Such a moderate level of stealthiness provides us with a good platform for the application of the sinusoidal PEG coating strategy to prolong the persistence of PM in the blood circulation.

PM showed a cumulant diameter of 112 nm with a polydispersity index (PDI) of 0.15 and an almost neutral -potential of 1.5 mV, suggesting the successful formation of the core-shell structure, composed of a PEG shell and a core containing condensed pDNA. First, PM loading Cy5-labeled pDNA was intravenously injected into the mice without two-arm-PEG-OligoLys injection for IVCLSM observation of PM behavior in the liver. PM showed sinusoidal entrapment as early as 5 min after injection, despite the fact that PM was PEGylated (Fig. 5, A and C). When two-arm-PEG-OligoLys was preinjected into the mice 5 min before the PM injection, the sinusoidal entrapment of the PM was effectively prevented even at 1 hour after injection (Fig. 5, B and D). This process was more obviously visualized by labeling both of two-arm-PEG-OligoLys and PM, using Alexa594 for two-arm-PEG-OligoLys and Cy5-labeled pDNA for PM (fig. S5 and movie S2). Meanwhile, under continuous observation, PM preinjected with two-arm-PEG-OligoLys exhibited sinusoidal attachment to some extent at 3 hours after injection. This result is consistent with the gradual clearance of two-arm-PEG-OligoLys from the sinusoidal wall 3 hours after injection (Fig. 3, B and D).

Two-arm-PEG-OligoLys was intravenously injected to coat liver sinusoidal wall with PEG, followed by the intravenous injection of PM loading pDNA 5 min later. (A and B) IVCLSM imaging of PM loading Cy5-labeled pDNA (red) in the liver without PEG coating of sinusoid (A) or with the coating (B). Intensity profiles of Cy5 in the white arrows in (A) and (B) are shown in (C) and (D), respectively [(C) without coating and (D) with coating]. (E) Blood circulation profiles of PM with or without PEG coating of sinusoidal wall. n = 4. (F) PM loading Luc-expressing pDNA was injected to tumor-bearing mice with or without preinjection of two-arm-PEG-OligoLys. Luc expression in the tumor was measured 2 days after injection. n = 4. Data are shown as means SEM. Statistical analysis was performed using unpaired two-tailed Students t test.

The effect of two-arm-PEG-OligoLys preinjection on PM clearance was further evaluated by observing the blood circulation profile of PM. Without two-arm-PEG-OligoLys preinjection, PM showed two phases of decrease in its blood concentration, with a rapid drop within 1 hour after injection, followed by a gradual decrease (Fig. 5E). The marked decrease in the PM blood concentration could be attributed to its tissue distribution, including the sinusoidal entrapment, as shown in Fig. 5, A and C. Such rapid PM clearance from the blood was effectively prevented by two-arm-PEG-OligoLys preinjection, presumably via the prevention of sinusoidal PM clearance, as shown in Fig. 5, B and D.

These promising results motivated us to use our strategy for gene transfection at the tumor site, as the PM formulation used in this study provided successful outcomes in the antiangiogenic treatment of cancer in our previous reports (41, 42). PM loading luciferase (Luc) pDNA was intravenously injected into the mice bearing C26 murine colon carcinoma, 5 min after preinjection of two-arm-PEG-OligoLys. Two-arm-PEG-OligoLys preinjection resulted in a more than 10-fold increase in Luc expression efficiency in the tumor compared with the PM injection without two-arm-PEG-OligoLys preinjection (Fig. 5F). The enhanced transfection expression efficiency of PM in the tumor after two-arm-PEG-OligoLys preinjection could be attributed to the avoidance of PM sinusoidal entrapment, which may result in enhanced tumor accumulation of PM.

Last, we applied the two-arm-PEG-OligoLys preinjection approach to the administration of viral gene vectors, in which this technology is highly demanded. In particular, when organs other than the liver are targeted, sinusoidal entrapment of the vectors seriously hinders the ability of viruses to reach their target organs (14, 24), resulting in an increase in the viral dose, which then poses a safety problem. Although AAV is widely believed to be safe, high levels of toxicity have been observed in large animals after AAV administration at the dose that is required to obtain therapeutic levels of protein expression in the spine (43). Here, two-arm-PEG-OligoLys preinjection was performed 5 min before injection with AAV8 to prevent the sinusoidal clearance of AAV8 and to relocate it to the heart and skeletal muscles, which are promising target organs for the therapeutic application of AAV8 (44). Three weeks after the delivery of AAV8 expressing Luc, two-arm-PEG-OligoLys preinjection resulted in a decrease in the expression efficiency of Luc in the liver to 42% of the level observed without two-arm-PEG-OligoLys preinjection (Fig. 6A). This result suggests the successful prevention of AAV8 entrapment in the liver by the PEG coating of the sinusoidal wall using two-arm-PEG-OligoLys. Two-arm-PEG-OligoLys preinjection resulted in a significant increase in Luc expression in AAV8 target organs, a 4.3-fold increase in the heart (Fig. 6B), and a 2.3-fold increase in the skeletal muscles (Fig. 6C), respectively, presumably via the relocation of AAV8 from the liver sinusoids to these organs after sinusoidal PEG coating. This result demonstrates the effectiveness of our strategy in increasing the gene expression of viral vectors in their target organs, which will allow for a reduction in the dose of the vectors needed for gene therapy, thereby minimizing the safety concerns.

Five minutes after intravenous injection of two-arm-PEG-OligoLys for PEG coating of liver sinusoidal wall, AAV8 expressing Luc was intravenously injected. Three weeks later, Luc expression in the liver (A), heart (B), and skeletal muscle (C) was measured. n = 6. Data are shown as means SEM. Statistical analysis was performed using unpaired two-tailed Students t test.

An important feature of two-arm-PEG-OligoLys for future clinical applications is its transient binding profile to the liver sinusoidal walls with a gradual clearance to the bile, providing an advantage in terms of safety over one-arm-PEG-OligoLys, which persisted in the sinusoidal wall. To obtain mechanistic insight into the differences between one- and two-arm-PEG-OligoLys, first, the intrinsic biliary excretion profile of OligoLys without PEGylation was observed in the liver using IVCLSM. Non-PEGylated OligoLys exhibited a high accumulation to the presumable location of bile canaliculi, especially 3 hours or more after injection (fig. S6). This result indicates that OligoLys is intrinsically cleared to the bile, while this process is inhibited by single 80-kDa PEG chain conjugation to OligoLys but not by double 40-kDa PEG chain conjugation. Meanwhile, both one- and two-arm-PEG-OligoLys exhibited similar behavior in terms of their binding to the sinusoidal wall after coinjection (Fig. 4). Thus, binding affinity to the sinusoidal wall may not be a major factor for the differences between one- and two-arm-PEG-OligoLys. Two-arm-PEG-OligoLys was cleared to the bile even after coinjection with one-arm-PEG-OligoLys, indicating that one-arm-PEG-OligoLys preserves the liver functionality of biliary clearance. Even under such conditions, one-arm-PEG-OligoLys still failed to be cleared.

Although detailed molecular analyses should be performed in the future to fully explain such clearance behavior of one- and two-arm-PEG-OligoLys, it is worth proposing a possible mechanism, based on the following two hypotheses. (i) Sinusoidal walls are densely coated with PEG. (ii) Biliary clearance of PEGylated OligoLys occurs via the endocytotic pathway, especially clathrin-mediated endocytosis, which is dominant in LSECs (11). On the basis of the radius of gyration, the diameter of 40-kDa and 80-kDa PEG is around 20 and 30 nm, respectively, which is close to the typical size of clathrin-coated vesicle (50 to 200 nm) (45, 46). When cell membrane is densely coated with PEG, such large PEG chains would overlap with each other after curving of cell membrane in endocytosis, and such overlapping between PEG exclusion volume is entropically unfavorable based on a scaling theory (47, 48). Here, we estimated the effect of PEG configuration on the overlapping volume using mathematical modeling, by assuming one-arm-PEG-OligoLys as one sphere of 80-kDa PEG and two-arm-PEG-OligoLys as two spheres of 40-kDa PEG, which densely coat the plasma membrane with a hexagonal lattice structure, without overlapping. In this model, curving of cell membrane in 50- to 200 nm-sized vesicles induces overlapping of PEG chains, with 80-kDa PEG providing more than threefold larger volume of the overlap compared with 40-kDa PEG (note S1). This calculation suggests that long single PEG chain (80 kDa) may not represent a suitable cargo of endocytotic vesicles to facilitate biliary excretion, while separation of PEG chains into two segments is effective in avoiding this issue.

Such transient coating of liver sinusoidal walls with two-arm-PEG-OligoLys allowed us to relocate nonviral and viral gene vectors from the sinusoidal wall to their target tissues, thereby improving the gene transfection efficiency in the tissues. With the ability to improve nanomedicine pharmacokinetics, this approach can be used not only to enhance the effect of nanomedicines but also to reduce the dose required to obtain these effects, which is particularly important for reducing the toxicity of viral gene therapy. While clearance behavior of two-arm-PEG-OligoLys was evaluated in detail after its single bolus administration as well as under the continuous infusion for several hours (fig. S3), detailed examination of possible chronic toxicity due to polymer overloading upon multiple injections may be required in the future to translate this procedure of transient surface covering of sinusoids in clinics, because nanomedicines are administered repeatedly in many cases. Here, we faithfully focus on the configuration of PEG (linear versus two-arm branched) having the same total Mw of 80 kDa, yet optimization of total PEG Mw should also be addressed in the future for further optimal tuning of the liver sinusoidal coating to maximize the efficacy of nanomedicine therapy, with minimal influence on liver physiological functions. Our approach is versatile for combinational use with various nanomedicines, including synthetic and nature-derived nanomedicines, opening avenues for future nanotherapy and nanodiagnosis.

OligoLys with or without PEGylation was synthesized via the ring-opening polymerization (ROP) of N-trifluoroacetyl-l-lysine N-carboxyanhydride [l-Lys(TFA)-NCA, Chuo Kaseihin Co. Inc., Tokyo, Japan], as previously described for two-arm-PEG-OligoLys (49), one-arm-PEG-OligoLys (50), and non-PEGylated OligoLys (51). Briefly, for two-arm-PEG-OligoLys synthesis, two-arm--methoxy--amino-PEG [two-arm-PEG-NH2, Mn (number-average molecular weight) = 2 40 kDa, NOF Corporation, Tokyo, Japan] was used as a macroinitiator for the ROP of l-Lys(TFA)-NCA to obtain two-arm-PEG-OligoLys(TFA). The molecular weight distribution (Mw/Mn) of two-arm-PEG-OligoLys(TFA) was 1.04, according to size exclusion chromatography (SEC) (TOSOH HLC-8220; Tosoh Corp., Tokyo, Japan). The TFA groups were deprotected to obtain two-arm-PEG-OligoLys. The degree of polymerization (DP) of OligoLys in two-arm-PEG-OligoLys was 19, according to 1H nuclear magnetic resonance (NMR) spectrum (JEOL ECS 400; JEOL, Tokyo, Japan). For one-arm-PEG-OligoLys synthesis, one-arm-PEG-OligoLys(TFA) was synthesized using one-arm--methoxy--amino-PEG (one-arm-PEG-NH2, Mn = 83 kDa) as a macroinitiator of ROP of l-Lys(TFA)-NCA and exhibited Mw/Mn of 1.06 in SEC analysis. One-arm-PEG-OligoLys, obtained after the deprotection of TFA groups, showed an OligoLys DP of 21 in 1H NMR. For non-PEGylated OligoLys synthesis, OligoLys(TFA) was synthesized by ROP of l-Lys(TFA)-NCA using n-butylamine (TCI Chemicals Co. Ltd., Tokyo, Japan) as an initiator, followed by the deprotection of TFA groups to obtain OligoLys. The DP of OligoLys was 28, according to the 1H NMR spectrum. The fluorescence labeling of OligoLys with or without PEGylation was performed as previously described (49). Briefly, one- and two-arm-PEG-OligoLys and non-PEGylated OligoLys were labeled with a single molecule of Alexa dye at OligoLys at the main chain end the -NH2 group before deprotecting the TFA groups using the N-hydroxysuccinimide (NHS) ester of Alexa Fluor 594 or 647 (Thermo Fischer Scientific, Waltham, MA, USA), according to the manufacturers instructions. For injection, OligoLys with or without PEGylation, with or without fluorescence labeling, was dissolved in 10 mM Hepes buffer containing 150 mM NaCl (pH 7.3).

All animal experimental procedures were approved and conducted in compliance with the Institutional Guidelines for the Care and Use of Laboratory Animals as stated by the Animal Committee of the Innovation Center of NanoMedicine (iCONM).

All of the intravital observations in this study were performed using IVCLSM, an A1R confocal laser scanning microscope (Nikon Corp., Tokyo, Japan), connected to an upright ECLIPSE FN1 (Nikon Corp.), using the following settings. The pinhole diameter was set to obtain a 10-m optical slice. BALB/c mice (6 weeks old, female, 18 to 20 g, Charles River Laboratories Inc., Yokohama, Japan) were anesthetized with 2.5% isoflurane (Abbott Japan Co. Ltd., Tokyo, Japan) using a NARCOBIT-E Univenter 400 Anaesthesia Unit (Natsume Seisakucho Co. Ltd., Tokyo, Japan). The anesthetized mice were placed onto a temperature-controlled plate (Thermoplate; Tokai Hit Co. Ltd., Shizuoka, Japan) with the temperature set to 37C.

For the observation of blood vessels in the earlobe dermis, the earlobe was fixed using a drop of immersion oil beneath the coverslip. For the observation of the liver, the liver was surgically exposed and glued directly to the cover glass using a drop of oil. Fluorescence-labeled OligoLys with or without PEGylation was intravenously injected through a catheter inserted into the lateral tail vein slowly in approximately 30 s at the dose of 15 nmol per mouse (1.25 mg per mouse for one- and two-arm-PEG-OligoLys and 0.05 mg per mouse for non-PEGylated OligoLys). Throughout the study, the autofluorescence signal of liver parenchyma was excited using a 405-nm laser and detected using a 450/50-nm bandpass emission filter. Alexa594 was excited using a 561-nm laser and detected using a 595/50 bandpass emission filter. Alexa647 was excited using a 640-nm laser and detected using a 700/50-nm bandpass emission filter. A 40 objective lens was used for liver imaging, while a 20 objective lens was used for earlobe imaging. Images were processed using NIS-Elements software (Nikon Corp.) for the quantification of fluorescence intensity. The fluorescence intensity of each pixel in the line charts was calculated after subtracting the background fluorescence intensity, which was measured using the images obtained 10 s before sample injection.

CF diacetate (CFDA, TCI Chemicals Co. Ltd.) was intravenously injected at a dose of 0.2 mg/kg. Five minutes later, a liver image was obtained using IVCLSM, by exciting CFDA using a 488-nm laser and detecting the fluorescence using a 520/50-nm bandpass emission filter. Immediately after the CFDA imaging, two-arm-PEG-OligoLys was intravenously injected for liver imaging 7 hours later, as described in the previous section.

The blood circulation profile of fluorescence-labeled OligoLys with or without PEGylation was quantified by measuring the fluorescence intensity of the blood vessel lumen in the earlobe after injection of the samples, as described in our previous report (49). Briefly, the fluorescence intensity in the region of interest (ROI) in the vein was measured at each time point, followed by the subtraction of the background fluorescence intensity obtained 10 s before the injection. The value obtained for each time point was standardized with the maximum fluorescence intensity of the ROI during the observation period.

In the coinjection of one- and two-arm-PEG-OligoLys, a mixture of 1.25 mg per mouse of Alexa647-labeled one-arm-PEG-OligoLys and 1.25 mg per mouse of Alexa594-labeled two-arm-PEG-OligoLys was injected from the tail vein. The parenchymal autofluorescence and fluorescence signal from Alexa594 and Alexa647 was detected as described in the Intravital observation of earlobe and liver section. After subtracting the background fluorescence intensity, which was measured using the images obtained 10 s before the sample injection, the fluorescence intensity of Alexa594 and Alexa647 was standardized on the basis of the intensity of fluorescence in the blood vessel lumen at 30 s after injection, set to 100% in Fig. 4 (B to D). The attachment of one- and two-arm-PEG-OligoLys to the sinusoidal wall was almost unobservable at 30 s after injection (Fig. 4, A and B).

OligoLys with or without PEGylation was injected into the tail vein at the same dose as for intravital imaging above (1.25 mg per mouse for one- and two-arm-PEG-OligoLys and 0.05 mg per mouse for non-PEGylated OligoLys). Blood was collected from the mice 4 hours after injection to examine the plasma using a DRI-CHEM 7000i system (Fujifilm, Tokyo, Japan).

Mouse blood was centrifuged at 500g for 5 min to sediment the blood cells, followed by washing with phosphate-buffered saline (PBS; pH 7.4) twice. Red blood cells (RBCs) collected from 1 ml of the blood were suspended in 20 ml of PBS. One volume of OligoLys with or without PEGylation was added to 10 volumes of the RBC suspension. The final concentration of OligoLys with or without PEGylation was adjusted to 7.5 pM, which is the same as the calculated concentration of OligoLys in the blood when OligoLys injected at the dose used in intravital imaging above was evenly distributed in 2 ml of mouse blood. The mixture was incubated at 37C for 1 hour, followed by centrifugation at 500g for 5 min. The absorbance of the supernatant at 405 nm was measured using Microplate Reader Infinite M1000 Pro (Tecan Japan Co. Ltd., Kanagawa, Japan) to quantify the amount of hemoglobin. A mixture of one volume of Triton X-100 (20% v/v) and 10 volumes of RBC suspension was sonicated for use as a positive control (exhibits 100% activity of hemolysis). The absorbance value of each sample was compared to the value obtained for the positive control.

PEG-PLys, used for constructing PM as described in the following section, was synthesized via ROP of l-Lys(TFA)-NCA using PEG-NH2 (Mn = 12 kDa) (NOF Corporation) as a macroinitiator. The Mw/Mn of PEG-PLys(TFA) was 1.05 according to SEC. The DP of PLys in PEG-PLys was 44, based on the 1H NMR spectrum. The 1-imino-4-mercaptobutyl (IM) groups were introduced onto the side-chain -amino groups of the lysine units of the PLys segment in PEG-PLys [PEG-PLys(IM)] using 2-iminothiolane (Thermo Fischer Scientific), according to a previous report (39). The introduction ratio of IM in the total NH2 groups in the original PEG-PLys was 50%, according to the 1H NMR.

A pDNA expressing Luc, pCAG-Luc2, was constructed by cloning the Luc coding sequence of pGL4.13 vector (Promega, Madison, WI, USA) into the pCAG-GS vector (RIKEN BioResource Research Center, Tsukuba, Japan). PM was prepared from PEG-PLys(IM) and pCAG-Luc2 pDNA at [amino groups in PEG-PLys(IM) (N)] to [phosphate groups in pDNA (P)] (N/P) ratio of 2, as previously reported (39).

The dynamic light scattering (DLS) and -potential measurements were measured using a Zetasizer Nano ZS ZEN3500 (Malvern Instruments Ltd., Worcestershire, UK). For these measurements, the pDNA concentration was adjusted to 33.3 g/ml, dissolved in 10 mM Hepes buffer containing 150 mM NaCl for DLS measurement and in 10 mM Hepes buffer without NaCl addition for -potential measurements. The hydrodynamic diameter (DH) and PDI of PM were evaluated using DLS at a detection angle of 173 and a temperature of 25C using cumulant methods. The -potential was measured with electrophoretic light scattering at 37C using Smoluchowskis equation.

For injection, the pDNA concentration was adjusted to 100 g/ml with a final concentration of Hepes and NaCl of 10 and 150 mM, respectively.

For the intravital imaging of PM, pCAG-Luc2 pDNA was labeled with Cy5 using the Label IT Tracker Intracellular Nucleic Acid Localization Kit (Mirus Bio Corp., Madison, WI). PM loading Cy5-labeled pCAG-Luc2 pDNA was intravenously injected into the tail vein at the dose of 20 g per mouse 5 min after the intravenous preinjection of two-arm-PEG-OligoLys at a dose of 1.25 mg per mouse. The control mice were injected with 10 mM Hepes buffer containing 150 mM NaCl (pH 7.3) instead of two-arm-PEG-OligoLys solution before PM injection. Liver imaging and the evaluation of the blood circulation profile were performed, as described in the Intravital observation of earlobe and liver and Evaluation of blood circulation profile sections, respectively.

Murine colon adenocarcinoma 26 (C26) cells were obtained from the National Cancer Center (Tokyo, Japan) and cultured in high-glucose Dulbeccos modified Eagles medium containing 10% fetal bovine serum. C26 cells (5 106 cells per mouse) were inoculated into subcutaneous tissue in the right rear flank of BALB/c nu/nu mice (7 weeks old, female, Charles River Laboratories). Mice with tumors of approximately 100 mm3 were intravenously injected with PM loading 20 g of pCAG-Luc2 pDNA, with or without two-arm-PEG-OligoLys preinjection, as described in the previous section. Tumors were harvested 48 hours after PM injection. The extracted tumor was homogenized using Multibeads Shocker in passive lysis buffer (Promega, Madison, WI, USA), followed by a Luc assay using a Luciferase Assay System (Promega) and Lumat LB9507 (Berthold Technologies, Bad Wildbad, Germany). The luminescence intensity values were normalized to the total protein amount in the homogenates determined by the Micro BCA Protein Assay Reagent Kit (Thermo Fischer Scientific). The values were presented after subtracting the background values obtained from the tumors harvested from mice without PM injection.

BALB/c mice (6 weeks old, female, Charles River Laboratories) were intravenously injected with 1.25 mg of two-arm-PEG-OligoLys, followed by the injection of AAV8 encoding firefly Luc driven by the CMV-IVS promoter (Vector Biolabs, Malvern, PA, USA) at the dose of 2.5 1011 viral genomes per mouse, sequentially at 5-min intervals. For the control mice, 10 mM Hepes buffer containing 150 mM NaCl (pH7.3), instead of two-arm-PEG-OligoLys, was injected before the AAV injection. Three weeks after AAV8 injection, the liver, heart, and muscles from the backside were excised. The Luc assay and data were analyzed as described in the previous section for the quantification of Luc expression in the tumor tissue.

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Acknowledgments: We thank M. Kuronuma and Y. Satoh (Kawasaki Institute of Industrial Promotion) for technical assistance. Funding: This research was supported financially by the Japan Science and Technology Agency (JST) through the Center of Innovation (COI) Program [Center of Open Innovation Network for Smart Health (COINS) (grant number JPMJCE1305)], Research on the Innovative Development and the Practical Application of New Drugs for Hepatitis B from the Japan Agency for Medical Research and Development (AMED) (JP17fk0310111 to K.K.), and Grants-in-Aid for Scientific Research (B) (18 K03529 to S.U.) and for Early-Career Scientist (18 K18393 to A.D.) from the Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT). Author contributions: A.D., S.U., and K.K conceived the idea, designed all the experiments, and wrote the manuscript. A.D. performed all the experiments. K.T. helped with the IVCLSM experiments. S.A. performed the pharmacokinetic analysis. H.K. assisted with the virus experiment. S.F. helped with synthesis of the oligocations. J.L., S.O., T.A.T., X.L., K.H., and Y.M. contributed in the other experiments. K.O. discussed the experimental data. S.U. and K.K. supervised the whole project. Competing interests: K.K. is a founder and a scientific advisor of AccuRna Inc. The remaining authors declare that they have no conflict of interests. PCT patent pending: Kawasaki Institute of Industrial Promotion (K.K., S.O., S.U., K.H., A.D., and K.T). Date: 12 March 2019; serial numbers: PCT/JP2019/009919. JP patent pending: Kawasaki Institute of Industrial Promotion (K.K., S.O., S.U., K.H., and K.O). Date: 19 November 2019; serial numbers: JP2019/520319. Data and materials availability: All experimental 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 are from the authors.

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Transient stealth coating of liver sinusoidal wall by anchoring two-armed PEG for retargeting nanomedicines - Science Advances