Category Archives: medicine

7th annual Vancouver Nanomedicine Day, Sept. 17, 2020

Like so many events these days (COVID-19 days), this event put on by Canada’s NanoMedicines Innovation Network (NMIN) will be held virtually. Here’s more from the ‘Virtual’ Vancouver Nanomedicine Day 2020 event page on the NMIN website,

This world-class symposium, the sixth event of its kind, will bring together a record number (1000+) of renowned Canadian and international experts from across the nanomedicines field to:

  • highlight the discoveries and innovations in nanomedicines that are contributing to global progress in acute, chronic and orphan disease treatment and management;
  • present up-to-date diagnostic and therapeutic  nanomedicine approaches to addressing the challenges of COVID-19; and
  • facilitate discussion among nanomedicine researchers and innovators and UBC and NMIN clinician-scientists, basic researchers, trainees, and research partners.

Since 2014, Vancouver Nanomedicine Day has advanced nanomedicine research, knowledge mobilization and commercialization in Canada by sharing high-impact findings and facilitating interaction—among researchers, postdoctoral fellows, graduate students, and life science and startup biotechnology companies—to catalyze research collaboration.

Here are a few highlights from the ‘Virtual’ Vancouver Nanomedicine Day 2020 event page,

  • An introduction to nanomedicines by Dr. Emmanuel Ho (University of Waterloo)
  • A keynote address by an iconic nanomedicine innovator: Dr. Robert Langer (MIT, Department of Chemical Engineering)
  • Invited talks by internationally renowned experts, including Dr. Vito Foderà (The University of Copenhagen, Denmark); Dr. Lucia Gemma Delogu (University of Padova, Italy); and Dr. Christine Allen (University of Toronto)
  • A virtual poster competition, with cash prizes for the top posters
  • A debate on whether “nanomedicines are still the next big thing” between Marcel Bally (proponent) and Kishor Wasan (opponent)

You can get the Program in PDF.

Registration is free. But you must Register.

Here’s the event poster,

[downloaded from https://www.nanomedicines.ca/nmd-2020/]

I have a few observations, First, Robert Langer is a big deal. Here are a few highlights from his Wikipedia entry (Note: Links have been removed),

Robert Samuel Langer, Jr. FREng[2] (born August 29, 1948) is an American chemical engineer, scientist, entrepreneur, inventor and one of the twelve Institute Professors at the Massachusetts Institute of Technology.[3]

Langer holds over 1,350 granted or pending patents.[3][29] He is one of the world’s most highly cited researchers, having authored nearly 1,500 scientific papers, and has participated in the founding of multiple technology companies.[30][31]

Langer is the youngest person in history (at 43) to be elected to all three American science academies: the National Academy of Sciences, the National Academy of Engineering and the Institute of Medicine. He was also elected as a charter member of National Academy of Inventors.[32] He was elected as an International Fellow[2] of the Royal Academy of Engineering[2] in 2010.

It’s all about commercializing the research—or is it?

(This second observation is a little more complicated and requires a little context.) The NMIN is one of Canada’s Networks of Centres of Excellence (who thought that name up? …sigh), from the NMIN About page,

NMIN is funded by the Government of Canada through the Networks of Centres of Excellence (NCE) Program.

The NCEs seem to be firmly fixed on finding pathways to commercialization (from the NCE About page) Note: All is not as it seems,

Canada’s global economic competitiveness [emphasis mine] depends on making new discoveries and transforming them into products, services [emphasis mine] and processes that improve the lives of Canadians. To meet this challenge, the Networks of Centres of Excellence (NCE) offers a suite of programs that mobilize Canada’s best research, development and entrepreneurial [emphasis mine] expertise and focus it on specific issues and strategic areas.

NCE programs meet Canada’s needs to focus a critical mass of research resources on social and economic challenges, commercialize [emphasis mine] and apply more of its homegrown research breakthroughs, increase private-sector R&D, [emphasis mine] and train highly qualified people. As economic [emphasis mine] and social needs change, programs have evolved to address new challenges.

Interestingly, the NCE is being phased out,

As per the December 2018 NCE Program news, funding for the Networks of Centres of Excellence (NCE) Program will be gradually transferred to the New Frontiers in Research Fund (NFRF).

The new agency, NFRF, appears to have a completely different mandate, from the NFRF page on the Canada Research Coordinating Committee webspace,

The Canada Research Coordinating Committee designed the New Frontiers in Research Fund (NFRF) following a comprehensive national consultation, which involved Canadian researchers, research administrators, stakeholders and the public. NFRF is administered by the Tri-agency Institutional Programs Secretariat, which is housed within the Social Sciences and Humanities Research Council (SSHRC), on behalf of Canada’s three research granting agencies: the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council and SSHRC.

The fund will invest $275 million over the next 5 years beginning in fiscal 2018-19, and $65 million ongoing, to fund international, interdisciplinary, fast-breaking and high-risk research.

NFRF is composed of three streams to support groundbreaking research.

  • Exploration generates opportunities for Canada to build strength in high-risk, high-reward and interdisciplinary research;
  • Transformation provides large-scale support for Canada to build strength and leadership in interdisciplinary and transformative research; and
  • International enhances opportunities for Canadian researchers to participate in research with international partners.

As you can see there’s no reference to commercialization or economic challenges.

Personally

Here at last is the second observation, I find it hard to believe that the government of Canada has given up on the idea of commercializing research and increasing the country’s economic competitiveness through research. Certainly, Langer’s virtual appearance at Vancouver Nanomedicine Day 2020, suggests that at least some corners of the Canadian research establishment are remaining staunchly entrepreneurial.

After all, the only Canadian government ministry with science in its name is this one: Innovation, Science and Economic Development Canada (ISED), as of Sept. 11, 2020.. (The other ‘science’ ministries are Natural Resources Canada, Environment and Climate Change Canada, Fisheries and Oceans Canada, Health Canada, and Agriculture and Agri-Food Canada.) ISED is not exactly subtle. Intriguingly the latest review on the state of science and technology in Canada was released on April 10, 2018 (from the April 10, 2018 Council of Canadian Academies CCA] news release),

Canada remains strong in research output and impact, capacity for R&D and innovation at risk: New expert panel report

While Canada is a highly innovative country, with a robust research base and thriving communities of technology start-ups, significant barriers—such as a lack of managerial skills, the experience needed to scale-up companies, and foreign acquisition of high-tech firms—often prevent the translation of innovation into wealth creation.[emphasis mine] The result is a deficit of technology companies growing to scale in Canada, and a loss of associated economic and social benefits.This risks establishing a vicious cycle, where successful companies seek growth opportunities elsewhere due to a lack of critical skills and experience in Canada guiding companies through periods of rapid expansion.

According to the CCA’s [2018 report] Summary webpage, it was Innovation, Science and Economic Development Canada which requested the report. (I wrote up a two-part commentary under one of my favourite titles: “The Hedy Lamarr of international research: Canada’s Third assessment of The State of Science and Technology and Industrial Research and Development in Canada.” Part 1 and Part 2)

I will be fascinated to watch the NFRF and science commercialization situations as they develop.

In the meantime, you can sign up for free to attend the ‘Virtual’ Vancouver Nanomedicine Day 2020.

Optical fibers made from marine algae

Apparently after you’ve finished imaging with your marine algae-based optical fibers, you can eat them. A July 24, 2020 news item on Nanowerk announces the new research,

An optical fiber made of agar has been produced at the University of Campinas (UNICAMP) in the state of São Paulo, Brazil. This device is edible, biocompatible and biodegradable. It can be used in vivo for body structure imaging, localized light delivery in phototherapy or optogenetics (e.g., stimulating neurons with light to study neural circuits in a living brain), and localized drug delivery.

Another possible application is the detection of microorganisms in specific organs, in which case the probe would be completely absorbed by the body after performing its function.

Caption: Edible, biocompatible and biodegradable, these fibers have potential for various medical applications. Credit: Eric Fujiwara

A July 24, 2020 Fundação de Amparo à Pesquisa dFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) do Estado de São Paulo press release on EurekAlert, which originated the news item, provides a few more details about the researches and the work,

The research project, which was supported by São Paulo Research Foundation – FAPESP, was led by Eric Fujiwara, a professor in UNICAMP’s School of Mechanical Engineering, and Cristiano Cordeiro, a professor in UNICAMP’s Gleb Wataghin Institute of Physics, in collaboration with Hiromasa Oku, a professor at Gunma University in Japan.

An article on the study is published) in Scientific Reports, an online journal owned by Springer Nature.

Agar, also called agar-agar, is a natural gelatin obtained from marine algae. Its composition consists of a mixture of two polysaccharides, agarose and agaropectin. “Our optical fiber is an agar cylinder with an external diameter of 2.5 millimeters [mm] and a regular inner arrangement of six 0.5 mm cylindrical airholes around a solid core. Light is confined owing to the difference between the refraction indices of the agar core and the airholes,” Fujiwara told.

“To produce the fiber, we poured food-grade agar into a mold with six internal rods placed lengthwise around the main axis,” he continued. “The gel distributes itself to fill the available space. After cooling, the rods are removed to form airholes, and the solidified waveguide is released from the mold. The refraction index and geometry of the fiber can be adapted by varying the composition of the agar solution and mold design, respectively.”

The researchers tested the fiber in different media, from air and water to ethanol and acetone, concluding that it is context-sensitive. “The fact that the gel undergoes structural changes in response to variations in temperature, humidity and pH makes the fiber suitable for optical sensing,” Fujiwara said.

Another promising application is its simultaneous use as an optical sensor and a growth medium for microorganisms. “In this case, the waveguide can be designed as a disposable sample unit containing the necessary nutrients. The immobilized cells in the device would be optically sensed, and the signal would be analyzed using a camera or spectrometer,” he said.

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About São Paulo Research Foundation (FAPESP)

The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at http://www.fapesp.br/en and visit FAPESP news agency at http://www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe.

As per my usual practice, here’s a link to and a citation for the paper,

Agarose-based structured optical fibre by Eric Fujiwara, Thiago D. Cabral, Miko Sato, Hiromasa Oku & Cristiano M. B. Cordeiro. Scientific Reports volume 10, Article number: 7035 (2020) DOI: https://doi.org/10.1038/s41598-020-64103-3 Published: 27 April 2020

This paper is open access.

Should you have a problem accessing the English language version of the FAPESP website, the Portuguese language version of the site seems more accessible (assuming you have the language skills).

Gold nanoparticles make a new promise: a non-invasive COVID-19 breathalyser

I believe that swab they stick up your nose to test for COVDI-19 is 10 inches long so it seems to me that discomfort or unpleasant are not the words that best describe the testing experience .

Hopefully, no one will have to find inadequate vocabulary for this new COVID-19 testing assuming that future trials are successful and they are able to put the technology into production. From an August 19, 2020 news item on Nanowerk,

Few people who have undergone nasopharyngeal swabs for coronavirus testing would describe it as a pleasant experience. The procedure involves sticking a long swab up the nose to collect a sample from the back of the nose and throat, which is then analyzed for SARS-CoV-2 RNA [ribonucleic acid] by the reverse-transcription polymerase chain reaction (RT-PCR).

Now, researchers reporting in [American Chemical Society] ACS Nano (“Multiplexed Nanomaterial-Based Sensor Array for Detection of COVID-19 in Exhaled Breath”) have developed a prototype device that non-invasively detected COVID-19 in the exhaled breath of infected patients.

An August 19, 2020 ACS news release (also received via email and on EurekAlert), which originated the news item, provides more technical details,

In addition to being uncomfortable, the current gold standard for COVID-19 testing requires RT-PCR, a time-consuming laboratory procedure. Because of backlogs, obtaining a result can take several days. To reduce transmission and mortality rates, healthcare systems need quick, inexpensive and easy-to-use tests. Hossam Haick, Hu Liu, Yueyin Pan and colleagues wanted to develop a nanomaterial-based sensor that could detect COVID-19 in exhaled breath, similar to a breathalyzer test for alcohol intoxication. Previous studies have shown that viruses and the cells they infect emit volatile organic compounds (VOCs) that can be exhaled in the breath.

The researchers made an array of gold nanoparticles linked to molecules that are sensitive to various VOCs. When VOCs interact with the molecules on a nanoparticle, the electrical resistance changes. The researchers trained the sensor to detect COVID-19 by using machine learning to compare the pattern of electrical resistance signals obtained from the breath of 49 confirmed COVID-19 patients with those from 58 healthy controls and 33 non-COVID lung infection patients in Wuhan, China. Each study participant blew into the device for 2-3 seconds from a distance of 1¬-2 cm. Once machine learning identified a potential COVID-19 signature, the team tested the accuracy of the device on a subset of participants. In the test set, the device showed 76% accuracy in distinguishing COVID-19 cases from controls and 95% accuracy in discriminating COVID-19 cases from lung infections. The sensor could also distinguish, with 88% accuracy, between sick and recovered COVID-19 patients. Although the test needs to be validated in more patients, it could be useful for screening large populations to determine which individuals need further testing, the researchers say.

The authors acknowledge funding from the Technion-Israel Institute of Technology.

Here’s a link to and a citation for the paper,

Multiplexed Nanomaterial-Based Sensor Array for Detection of COVID-19 in Exhaled Breath by Benjie Shan, Yoav Y Broza, Wenjuan Li, Yong Wang, Sihan Wu, Zhengzheng Liu, Jiong Wang, Shuyu Gui, Lin Wang, Zhihong Zhang, Wei Liu, Shoubing Zhou, Wei Jin, Qianyu Zhang, Dandan Hu, Lin Lin, Qiujun Zhang, Wenyu Li, Jinquan Wang, Hu Liu, Yueyin Pan, and Hossam Haick. ACS Nano 2020, XXXX, XXX, XXX-XXX DOI: https://doi.org/10.1021/acsnano.0c05657 Publication Date:August 18, 2020 Copyright © 2020 American Chemical Society

This paper is behind a paywall.

Shining a light on flurocarbon bonds and robotic ‘soft’ matter research

Both of these news bits are concerned with light for one reason or another.

Rice University (Texas, US) and breaking fluorocarbon bonds

The secret to breaking fluorocarbon bonds is light according to a June 22, 2020 news item on Nanowerk,

Rice University engineers have created a light-powered catalyst that can break the strong chemical bonds in fluorocarbons, a group of synthetic materials that includes persistent environmental pollutants.

A June 22, 2020 Rice University news release (also on EurekAlert), which originated the news item, describes the work in greater detail,

In a study published this month in Nature Catalysis, Rice nanophotonics pioneer Naomi Halas and collaborators at the University of California, Santa Barbara (UCSB) and Princeton University showed that tiny spheres of aluminum dotted with specks of palladium could break carbon-fluorine (C-F) bonds via a catalytic process known as hydrodefluorination in which a fluorine atom is replaced by an atom of hydrogen.

The strength and stability of C-F bonds are behind some of the 20th century’s most recognizable chemical brands, including Teflon, Freon and Scotchgard. But the strength of those bonds can be problematic when fluorocarbons get into the air, soil and water. Chlorofluorocarbons, or CFCs, for example, were banned by international treaty in the 1980s after they were found to be destroying Earth’s protective ozone layer, and other fluorocarbons were on the list of “forever chemicals” targeted by a 2001 treaty.

“The hardest part about remediating any of the fluorine-containing compounds is breaking the C-F bond; it requires a lot of energy,” said Halas, an engineer and chemist whose Laboratory for Nanophotonics (LANP) specializes in creating and studying nanoparticles that interact with light.

Over the past five years, Halas and colleagues have pioneered methods for making “antenna-reactor” catalysts that spur or speed up chemical reactions. While catalysts are widely used in industry, they are typically used in energy-intensive processes that require high temperature, high pressure or both. For example, a mesh of catalytic material is inserted into a high-pressure vessel at a chemical plant, and natural gas or another fossil fuel is burned to heat the gas or liquid that’s flowed through the mesh. LANP’s antenna-reactors dramatically improve energy efficiency by capturing light energy and inserting it directly at the point of the catalytic reaction.

In the Nature Catalysis study, the energy-capturing antenna is an aluminum particle smaller than a living cell, and the reactors are islands of palladium scattered across the aluminum surface. The energy-saving feature of antenna-reactor catalysts is perhaps best illustrated by another of Halas’ previous successes: solar steam. In 2012, her team showed its energy-harvesting particles could instantly vaporize water molecules near their surface, meaning Halas and colleagues could make steam without boiling water. To drive home the point, they showed they could make steam from ice-cold water.

The antenna-reactor catalyst design allows Halas’ team to mix and match metals that are best suited for capturing light and catalyzing reactions in a particular context. The work is part of the green chemistry movement toward cleaner, more efficient chemical processes, and LANP has previously demonstrated catalysts for producing ethylene and syngas and for splitting ammonia to produce hydrogen fuel.

Study lead author Hossein Robatjazi, a Beckman Postdoctoral Fellow at UCSB who earned his Ph.D. from Rice in 2019, conducted the bulk of the research during his graduate studies in Halas’ lab. He said the project also shows the importance of interdisciplinary collaboration.

“I finished the experiments last year, but our experimental results had some interesting features, changes to the reaction kinetics under illumination, that raised an important but interesting question: What role does light play to promote the C-F breaking chemistry?” he said.

The answers came after Robatjazi arrived for his postdoctoral experience at UCSB. He was tasked with developing a microkinetics model, and a combination of insights from the model and from theoretical calculations performed by collaborators at Princeton helped explain the puzzling results.

“With this model, we used the perspective from surface science in traditional catalysis to uniquely link the experimental results to changes to the reaction pathway and reactivity under the light,” he said.

The demonstration experiments on fluoromethane could be just the beginning for the C-F breaking catalyst.

“This general reaction may be useful for remediating many other types of fluorinated molecules,” Halas said.

Caption: An artist’s illustration of the light-activated antenna-reactor catalyst Rice University engineers designed to break carbon-fluorine bonds in fluorocarbons. The aluminum portion of the particle (white and pink) captures energy from light (green), activating islands of palladium catalysts (red). In the inset, fluoromethane molecules (top) comprised of one carbon atom (black), three hydrogen atoms (grey) and one fluorine atom (light blue) react with deuterium (yellow) molecules near the palladium surface (black), cleaving the carbon-fluorine bond to produce deuterium fluoride (right) and monodeuterated methane (bottom). Credit: H. Robatjazi/Rice University

Here’s a link to and a citation for the paper,

Plasmon-driven carbon–fluorine (C(sp3)–F) bond activation with mechanistic insights into hot-carrier-mediated pathways by Hossein Robatjazi, Junwei Lucas Bao, Ming Zhang, Linan Zhou, Phillip Christopher, Emily A. Carter, Peter Nordlander & Naomi J. Halas. Nature Catalysis (2020) DOI: https://doi.org/10.1038/s41929-020-0466-5 Published: 08 June 2020

This paper is behind a paywall.

Northwestern University (Illinois, US) brings soft robots to ‘life’

This June 22, 2020 news item on ScienceDaily reveals how scientists are getting soft robots to mimic living creatures,

Northwestern University researchers have developed a family of soft materials that imitates living creatures.

When hit with light, the film-thin materials come alive — bending, rotating and even crawling on surfaces.

A June 22, 2020 Northwestern University news release (also on EurekAlert) by Amanda Morris, which originated the news item, delves further into the details,

Called “robotic soft matter by the Northwestern team,” the materials move without complex hardware, hydraulics or electricity. The researchers believe the lifelike materials could carry out many tasks, with potential applications in energy, environmental remediation and advanced medicine.

“We live in an era in which increasingly smarter devices are constantly being developed to help us manage our everyday lives,” said Northwestern’s Samuel I. Stupp, who led the experimental studies. “The next frontier is in the development of new science that will bring inert materials to life for our benefit — by designing them to acquire capabilities of living creatures.”

The research will be published on June 22 [2020] in the journal Nature Materials.

Stupp is the Board of Trustees Professor of Materials Science and Engineering, Chemistry, Medicine and Biomedical Engineering at Northwestern and director of the Simpson Querrey Institute He has appointments in the McCormick School of Engineering, Weinberg College of Arts and Sciences and Feinberg School of Medicine. George Schatz, the Charles E. and Emma H. Morrison Professor of Chemistry in Weinberg, led computer simulations of the materials’ lifelike behaviors. Postdoctoral fellow Chuang Li and graduate student Aysenur Iscen, from the Stupp and Schatz laboratories, respectively, are co-first authors of the paper.

Although the moving material seems miraculous, sophisticated science is at play. Its structure comprises nanoscale peptide assemblies that drain water molecules out of the material. An expert in materials chemistry, Stupp linked the peptide arrays to polymer networks designed to be chemically responsive to blue light.

When light hits the material, the network chemically shifts from hydrophilic (attracts water) to hydrophobic (resists water). As the material expels the water through its peptide “pipes,” it contracts — and comes to life. When the light is turned off, water re-enters the material, which expands as it reverts to a hydrophilic structure.

This is reminiscent of the reversible contraction of muscles, which inspired Stupp and his team to design the new materials.

“From biological systems, we learned that the magic of muscles is based on the connection between assemblies of small proteins and giant protein polymers that expand and contract,” Stupp said. “Muscles do this using a chemical fuel rather than light to generate mechanical energy.”

For Northwestern’s bio-inspired material, localized light can trigger directional motion. In other words, bending can occur in different directions, depending on where the light is located. And changing the direction of the light also can force the object to turn as it crawls on a surface.

Stupp and his team believe there are endless possible applications for this new family of materials. With the ability to be designed in different shapes, the materials could play a role in a variety of tasks, ranging from environmental clean-up to brain surgery.

“These materials could augment the function of soft robots needed to pick up fragile objects and then release them in a precise location,” he said. “In medicine, for example, soft materials with ‘living’ characteristics could bend or change shape to retrieve blood clots in the brain after a stroke. They also could swim to clean water supplies and sea water or even undertake healing tasks to repair defects in batteries, membranes and chemical reactors.”

Fascinating, eh? No batteries, no power source, just light to power movement. For the curious, here’s a link to and a citation for the paper,

Supramolecular–covalent hybrid polymers for light-activated mechanical actuation by Chuang Li, Aysenur Iscen, Hiroaki Sai, Kohei Sato, Nicholas A. Sather, Stacey M. Chin, Zaida Álvarez, Liam C. Palmer, George C. Schatz & Samuel I. Stupp. Nature Materials (2020) DOI: https://doi.org/10.1038/s41563-020-0707-7 Published: 22 June 2020

This paper is behind a paywall.

World’s first liquid retina prosthesis

The new artificial liquid retina is biomimetic and consists of an aqueous component in which photoactive polymeric nanoparticles (whose size is of 350 nanometres, thus about 1/100 of the diameter of a hair) are suspended, going to replace the damaged photoreceptors. Credit: IIT-Istituto Italiano di Tecnologia [image downloaded from https://www.medgadget.com/2020/06/injectable-liquid-prosthesis-to-treat-retinal-diseases-developed.html]

A June 29, 2020 news item on Nanowerk announces the world’s first liquid retina prosthesis,

Researchers at IIT-Istituto Italiano di Tecnologia (Italian Institute of Technology) has led to the revolutionary development of an artificial liquid retinal prosthesis to counteract the effects of diseases such as retinitis pigmentosa and age-related macular degeneration that cause the progressive degeneration of photoreceptors of the retina, resulting in blindness.

The multidisciplinary team is composed by researchers from the IIT’s Center for Synaptic Neuroscience and Technology in Genoa coordinated by Fabio Benfenati and a team from the IIT’s Center for Nano Science and Technology in Milan coordinated by Guglielmo Lanzani, and it also involves the IRCCS Ospedale Sacrocuore Don Calabria in Negrar (Verona) with the team lead by Grazia Pertile, the IRCCS Ospedale Policlinico San Martino in Genoa and the CNR in Bologna. The research has been supported by Fondazione 13 Marzo Onlus, Fondazione Ra.Mo., Rare Partners srl and Fondazione Cariplo.

The study represents the state of the art in retinal prosthetics and is an evolution of the planar artificial retinal model developed by the same team in 2017 and based on organic semiconductor materials (Nature Materials 2017, 16: 681-689).

A June 30, 2020 IIT-Istituto Italiano di Tecnologia (Italian Institute of Technology) press release (also on EurekAlert but published June 29, 2020) provides more detail,

The “second generation” artificial retina is biomimetic, offers high spatial resolution and consists of an aqueous component in which photoactive polymeric nanoparticles (whose size is of 350 nanometres, thus about 1/100 of the diameter of a hair) are suspended, going to replace the damaged photoreceptors.

The experimental results show that the natural light stimulation of nanoparticles, in fact, causes the activation of retinal neurons spared from degeneration, thus mimicking the functioning of photoreceptors in healthy subjects.

Compared to other existing approaches, the new liquid nature of the prosthesis ensures fast and less traumatic surgery that consist of microinjections of nanoparticles directly under the retina, where they remain trapped and replace the degenerated photoreceptors; this method also ensures an increased effectiveness.

The data collected show also that the innovative experimental technique represents a valid alternative to the methods used to date to restore the photoreceptive capacity of retinal neurons while preserving their spatial resolution, laying a solid foundation for future clinical trials in humans. Moreover, the development of these photosensitive nanomaterials opens the way to new future applications in neuroscience and medicine.

“Our experimental results highlight the potential relevance of nanomaterials in the development of second-generation retinal prostheses to treat degenerative retinal blindness, and represents a major step forward” Fabio Benfenati commented. “The creation of a liquid artificial retinal implant has great potential to ensure a wide-field vision and high-resolution vision. Enclosing the photoactive polymers in particles that are smaller than the photoreceptors, increases the active surface of interaction with the retinal neurons, allows to easily cover the entire retinal surface and to scale the photoactivation at the level of a single photoreceptor.”

“In this research we have applied nanotechnology to medicine” concludes Guglielmo Lanzani. “In particular in our labs we have realized polymer nanoparticles that behave like tiny photovoltaic cells, based on carbon and hydrogen, fundamental components of the biochemistry of life. Once injected into the retina, these nanoparticles form small aggregates the size of which is comparable to that of neurons, that effectively behave like photoreceptors.”

“The surgical procedure for the subretinal injection of photoactive nanoparticles is minimally invasive and potentially replicable over time, unlike planar retinal prostheses” adds Grazia Pertile, Director at Operating Unit of Ophthalmology at IRCCS Ospedale Sacro Cuore Don Calabria. “At the same time maintaining the advantages of polymeric prosthesis, which is naturally sensitive to the light entering the eye and does not require glasses, cameras or external energy sources.”

The research study is based on preclinical models and further experimentations will be fundamental to make the technique a clinical treatment for diseases such as retinitis pigmentosa and age-related macular degeneration.

Here’s a link to and a citation for the paper,

Subretinally injected semiconducting polymer nanoparticles rescue vision in a rat model of retinal dystrophy by José Fernando Maya-Vetencourt, Giovanni Manfredi, Maurizio Mete, Elisabetta Colombo, Mattia Bramini, Stefano Di Marco, Dmytro Shmal, Giulia Mantero, Michele Dipalo, Anna Rocchi, Mattia L. DiFrancesco, Ermanno D. Papaleo, Angela Russo, Jonathan Barsotti, Cyril Eleftheriou, Francesca Di Maria, Vanessa Cossu, Fabio Piazza, Laura Emionite, Flavia Ticconi, Cecilia Marini, Gianmario Sambuceti, Grazia Pertile, Guglielmo Lanzani & Fabio Benfenati. Nature Nanotechnology (2020) DOI: https://doi.org/10.1038/s41565-020-0696-3 Published: 29 June 2020

This paper is behind a paywall.

Preventing warmed-up vaccines from becoming useless

One of the major problems with vaccines is that they need to be refrigerated. (The Nanopatch, which additionally wouldn’t require needles or syringes, is my favourite proposed solution and it comes from Australia.) This latest research into making vaccines more long-lasting is from the UK and takes a different approach to the problem.

From a June 8, 2020 news item on phys.org,

Vaccines are notoriously difficult to transport to remote or dangerous places, as they spoil when not refrigerated. Formulations are safe between 2°C and 8°C, but at other temperatures the proteins start to unravel, making the vaccines ineffective. As a result, millions of children around the world miss out on life-saving inoculations.

However, scientists have now found a way to prevent warmed-up vaccines from degrading. By encasing protein molecules in a silica shell, the structure remains intact even when heated to 100°C, or stored at room temperature for up to three years.

The technique for tailor-fitting a vaccine with a silica coat—known as ensilication—was developed by a Bath [University] team in collaboration with the University of Newcastle. This pioneering technology was seen to work in the lab two years ago, and now it has demonstrated its effectiveness in the real world too.

Here’s the lead researcher describing her team’s work

Ensilication: success in animal trials from University of Bath on Vimeo.

A June 8, 2020 University of Bath press release (also on EurekAlert) fills in more details about the research,

In their latest study, published in the journal Scientific Reports, the researchers sent both ensilicated and regular samples of the tetanus vaccine from Bath to Newcastle by ordinary post (a journey time of over 300 miles, which by post takes a day or two). When doses of the ensilicated vaccine were subsequently injected into mice, an immune response was triggered, showing the vaccine to be active. No immune response was detected in mice injected with unprotected doses of the vaccine, indicating the medicine had been damaged in transit.

Dr Asel Sartbaeva, who led the project from the University of Bath’s Department of Chemistry, said: “This is really exciting data because it shows us that ensilication preserves not just the structure of the vaccine proteins but also the function – the immunogenicity.”

“This project has focused on tetanus, which is part of the DTP (diphtheria, tetanus and pertussis) vaccine given to young children in three doses. Next, we will be working on developing a thermally-stable vaccine for diphtheria, and then pertussis. Eventually we want to create a silica cage for the whole DTP trivalent vaccine, so that every child in the world can be given DTP without having to rely on cold chain distribution.”

Cold chain distribution requires a vaccine to be refrigerated from the moment of manufacturing to the endpoint destination.

Silica is an inorganic, non-toxic material, and Dr Sartbaeva estimates that ensilicated vaccines could be used for humans within five to 15 years. She hopes the technology to silica-wrap proteins will eventually be adopted to store and transport all childhood vaccines, as well as other protein-based products, such as antibodies and enzymes.

“Ultimately, we want to make important medicines stable so they can be more widely available,” she said. “The aim is to eradicate vaccine-preventable diseases in low income countries by using thermally stable vaccines and cutting out dependence on cold chain.”

Currently, up to 50% of vaccine doses are discarded before use due to exposure to suboptimal temperatures. According to the World Health Organisation (WHO), 19.4 million infants did not receive routine life-saving vaccinations in 2018.

Here’s a link to and a citation for the paper,

Ensilicated tetanus antigen retains immunogenicity: in vivo study and time-resolved SAXS characterization by A. Doekhie, R. Dattani, Y-C. Chen, Y. Yang, A. Smith, A. P. Silve, F. Koumanov, S. A. Wells, K. J. Edler, K. J. Marchbank, J. M. H. van den Elsen & A. Sartbaeva. Scientific Reports volume 10, Article number: 9243 (2020) DOI: https://doi.org/10.1038/s41598-020-65876-3 Published 08 June 2020

This paper is open access

Nanopatch update

I tend to lose track as a science gets closer to commercialization since the science news becomes business news and I almost never scan that sector. It’s been about two-and-half years since I featured research that suggested Nanopatch provided more effective polio vaccination than the standard needle and syringe method in a December 20, 2017 post. The latest bits of news have an interesting timeline.

March 2020

Mark Kendal (Wikipedia entry) is the researcher behind the Nanopatch. He’s interviewed in a March 5, 2020 episode (about 20 mins.) in the Pioneers Series (bankrolled by Rolex [yes, the watch company]) on Monocle.com. Coincidentally or not, a new piece of research funded by Vaxxas (the nanopatch company founded by Mark Kendall; on the website you will find a ‘front’ page and a ‘Contact us’ page only) was announced in a March 17, 2020 news item on medical.net,

Vaxxas, a clinical-stage biotechnology company commercializing a novel vaccination platform, today announced the publication in the journal PLoS Medicine of groundbreaking clinical research indicating the broad immunological and commercial potential of Vaxxas’ novel high-density microarray patch (HD-MAP). Using influenza vaccine, the clinical study of Vaxxas’ HD-MAP demonstrated significantly enhanced immune response compared to vaccination by needle/syringe. This is the largest microarray patch clinical vaccine study ever performed.

“With vaccine coated onto Vaxxas HD-MAPs shown to be stable for up to a year at 40°C [emphasis mine], we can offer a truly differentiated platform with a global reach, particularly into low and middle income countries or in emergency use and pandemic situations,” said Angus Forster, Chief Development and Operations Officer of Vaxxas and lead author of the PLoS Medicine publication. “Vaxxas’ HD-MAP is readily fabricated by injection molding to produce a 10 x 10 mm square with more than 3,000 microprojections that are gamma-irradiated before aseptic dry application of vaccine to the HD-MAP’s tips. All elements of device design, as well as coating and QC, have been engineered to enable small, modular, aseptic lines to make millions of vaccine products per week.”

The PLoS publication reported results and analyses from a clinical study involving 210 clinical subjects [emphasis mine]. The clinical study was a two-part, randomized, partially double-blind, placebo-controlled trial conducted at a single Australian clinical site. The clinical study’s primary objective was to measure the safety and tolerability of A/Singapore/GP1908/2015 H1N1 (A/Sing) monovalent vaccine delivered by Vaxxas HD-MAP in comparison to an uncoated Vaxxas HD-MAP and IM [intramuscular] injection of a quadrivalent seasonal influenza vaccine (QIV) delivering approximately the same dose of A/Sing HA protein. Exploratory outcomes were: to evaluate the immune responses to HD-MAP application to the forearm with A/Sing at 4 dose levels in comparison to IM administration of A/Sing at the standard 15 μg HA per dose per strain, and to assess further measures of immune response through additional assays and assessment of the local skin response via punch biopsy of the HD-MAP application sites. Local skin response, serological, mucosal and cellular immune responses were assessed pre- and post-vaccination.

Here’s a link to and a citation for the latest ‘nanopatch’ paper,

Safety, tolerability, and immunogenicity of influenza vaccination with a high-density microarray patch: Results from a randomized, controlled phase I clinical trial by Angus H. Forster, Katey Witham, Alexandra C. I. Depelsenaire, Margaret Veitch, James W. Wells, Adam Wheatley, Melinda Pryor, Jason D. Lickliter, Barbara Francis, Steve Rockman, Jesse Bodle, Peter Treasure, Julian Hickling, Germain J. P. Fernando. DOI: https://doi.org/10.1371/journal.pmed.1003024 PLOS (Public Library of Science) Published: March 17, 2020

This is an open access paper.

May 2020

Two months later, Merck, an American multinational pharmaceutical company, showed some serious interest in the ‘nanopatch’. A May 28, 2020 article by Chris Newmarker for drugdelvierybusiness.com announces the news (Note: Links have been removed),

Merck has exercised its option to use Vaxxas‘ High Density Microarray Patch (HD-MAP) platform as a delivery platform for a vaccine candidate, the companies announced today [Thursday, May 28, 2020].

Also today, Vaxxas announced that German manufacturing equipment maker Harro Höfliger will help Vaxxas develop a high-throughput, aseptic manufacturing line to make vaccine products based on Vaxxas’ HD-MAP technology. Initial efforts will focus on having a pilot line operating in 2021 to support late-stage clinical studies — with a goal of single, aseptic-based lines being able to churn out 5 million vaccine products a week.

“A major challenge in commercializing microarray patches — like Vaxxas’ HD-MAP — for vaccination is the ability to manufacture at industrially-relevant scale, while meeting stringent sterility and quality standards. Our novel device design along with our innovative vaccine coating and quality verification technologies are an excellent fit for integration with Harro Höfliger’s aseptic process automation platforms. Adopting a modular approach, it will be possible to achieve output of tens-of-millions of vaccine-HD-MAP products per week,” Hoey [David L. Hoey, President and CEO of Vaxxas] said.

Vaxxas also claims that the patches can deliver vaccine more efficiently — a positive when people around the world are clamoring for a vaccine against COVID-19. The company points to a recent [March 17, 2020] clinical study in which their micropatch delivering a sixth of an influenza vaccine dose produced an immune response comparable to a full dose by intramuscular injection. A two-thirds dose by HD-MAP generated significantly faster and higher overall antibody responses.

As I noted earlier, this is an interesting timeline.

Final comment

In the end, what all of this means is that there may be more than one way to deal with vaccines and medicines that deteriorate all too quickly unless refrigerated. I wish all of these researchers the best.

Antiviral, antibacterial surface for reducing spread of infectious diseases

In the past several years, scientists have created antibacterial surfaces by fabricating materials with specific types of nanostructures. According to a May 27, 2020 news item on Nanowerk, scientists have now been able to add antiviral properties (Note: A link has been removed),

The novel coronavirus pandemic has caused an increased demand for antimicrobial treatments that can keep surfaces clean, particularly in health care settings. Although some surfaces have been developed that can combat bacteria, what’s been lacking is a surface that can also kill off viruses.

Now, researchers have found a way to impart durable antiviral and antibacterial properties to an aluminum alloy used in hospitals, according to a report in ACS Biomaterials Science & Engineering (“Antiviral and Antibacterial Nanostructured Surfaces with Excellent Mechanical Properties for Hospital Applications”).

A May 27, 2020 American Chemical Society (ACS) news release (also on EurekAlert), which originated the news item, describes the problem and the proposed solution,

Among other mechanisms, viruses and bacteria can spread when a person touches a site where germs have settled, such as a doorframe, handrail or medical device. A healthy person can often fight off these bugs, but hospital patients can be more vulnerable to infection. The number of hospital-acquired infections has been on the decline in the U.S., but they still cause tens of thousands of deaths every year, according to the U.S. Department of Health and Human Services. Chemical disinfectants or coatings containing hydrophobic compounds, silver ions or copper can reduce infectious contaminants on surfaces, but these treatments don’t last. However, nature has developed its own solutions for battling microorganisms, including microscopic structural features that render some insect wings lethal to bacteria. Scientists have replicated this effect by forming surfaces covered with minute pillars and other shapes that distort and kill bacterial cells. But Prasad Yarlagadda and colleagues wanted to inactivate viruses as well as bacteria, so they set out to generate a novel nanoscale topography on long-lasting, industrially relevant materials.

The team experimented with disks of aluminum 6063, which is used in doorframes, window panels, and hospital and medical equipment. Etching the disks with sodium hydroxide for up to 3 hours changed the initially smooth, hydrophobic surface into a ridged, hydrophilic surface. Bacteria or viruses were then applied to the etched disks. Most of the Pseudomonas aeruginosa and Staphylococcus aureus bacteria were inactivated after 3 hours on the surface, while viability of common respiratory viruses dropped within 2 hours; both results were better than with plastic or smooth aluminum surfaces. The disks retained their effectiveness even after tests designed to mimic hospital wear and tear. The researchers note this is the first report to show combined antibacterial and antiviral properties of a durable, nanostructured surface that has the potential to stop the spread of infections arising from physical surfaces in hospitals. This strategy could be extended to surfaces in other public areas, such as cruise ships, planes and airports, they say. The team is now studying the effects of their nano-textured aluminum surfaces on the novel coronavirus.

This approach reminds me of Sharklet, a company fabricating a material designed to mimic a shark’s skin which is naturally antibacterial due to the nanostructures on its skin (see my September 18, 2014 posting).

More about Sharklet later. First, here’s a link to and a citation for the paper about this latest work,

Antiviral and Antibacterial Nanostructured Surfaces with Excellent Mechanical Properties for Hospital Applications by Jafar Hasan, Yanan Xu, Tejasri Yarlagadda, Michael Schuetz, Kirsten Spann, and Prasad KDV Yarlagadda. ACS Biomater. Sci. Eng. 2020, XXXX, XXX, XXX-XXX DOI: https://doi.org/10.1021/acsbiomaterials.0c00348 Publication Date:May 7, 2020 Copyright © 2020 American Chemical Society

This paper is behind a paywall.

Business and science: a Sharklet update

You can find the Sharklet website here. I wasn’t able to find any news about recent business deals other than the company’s acquisition by Peaceful Union in May 2017. From a May 17, 2017 Sharklet news release on Business Wire (and on the company website here),

Sharklet Technologies, Inc., a biotechnology company lauded for the creation and commercialization of Sharklet®, the world’s first micro-texture that inhibits bacterial growth on surfaces, has announced that it has completed a financing event led by Peaceful Union, an equity medical device firm in Hangzhou, China. Terms of the transaction were not disclosed.

The acquisition of the company will enable Sharklet Technologies to accelerate the development of Sharklet for medical devices where chemical-free bacterial inhibition is desired as well as high-touch surfaces prone to bacterial contamination. The company also will accelerate development of a newly enhanced wound dressing technology to encourage healing.

Joe Bagan and Mark Spiecker led the transaction structure. “This is an important day for the company and investors,” said Joe Bagan, former board chair, and Mark Spiecker, former CEO. “Our investors will realize a significant transaction while enabling the company to accelerate growth.”

In concert with the investment, Sharklet Technologies founding member, chief technology officer, and Sharklet inventor Dr. Anthony Brennan, will become chairman of the board assuming duties from chairman Joe Bagan and CEO Mark Spiecker.

Interestingly, Bagan and Spiecker are Chief Executive Officer (CEO) and President, respectively at STAQ Pharma. I wonder if there are plans to sell this company too.

Getting back to Sharklet, I found two items of recent origin about business but I cannot speak to the accuracy or trustworthiness of either item. That said, you will find they provide some detail about Sharklet’s new business directions and new business ties.

While Sharklet’s current business associations have a sketchy quality, it seems that’s not unusual in business, especially where new technologies are concerned. For example, the introduction of electricity into homes and businesses was a tumultuous affair as the 2008 book, ‘Power Struggles; Scientific Authority and the Creation of Practical Electricity Before Edison’ by Michael Brian Schiffer makes clear, from the MIT [Massachusetts Institute of Technology] Press ‘Power Struggles’ webpage,

In 1882, Thomas Edison and his Edison Electric Light Company unveiled the first large-scale electrical system in the world to light a stretch of offices in a city. … After laying out a unified theoretical framework for understanding technological change, Schiffer presents a series of fascinating case studies of pre-Edison electrical technologies, including Volta’s electrochemical battery, the blacksmith’s electric motor, the first mechanical generators, Morse’s telegraph, the Atlantic cable, and the lighting of the Capitol dome. Schiffer discusses claims of “practicality” and “impracticality” (sometimes hotly contested) made for these technologies, and examines the central role of the scientific authority—in particular, the activities of Joseph Henry, mid-nineteenth-century America’s foremost scientist—in determining the fate of particular technologies. These emerging electrical technologies formed the foundation of the modern industrial world. Schiffer shows how and why they became commercial products in the context of an evolving corporate capitalism in which conflicting judgments of practicality sometimes turned into power struggles. [emphases mine]

Even given that the book’s focus is pre-Edison electricity, how do you mention Edison himself without even casually mentioning Nikola Tesla and George Westinghouse in the book’s overview? Getting back to my point, emerging technologies do not emerge easily.

Tiny sponges lure coronavirus away from lung cells

This research approach looks promising as three news releases trumpeting the possibilities indicate. First, there’s the June 17, 2020 American Chemical Society (ACS) news release,

Scientists are working overtime to find an effective treatment for COVID-19, the illness caused by the new coronavirus, SARS-CoV-2. Many of these efforts target a specific part of the virus, such as the spike protein. Now, researchers reporting in Nano Letters have taken a different approach, using nanosponges coated with human cell membranes –– the natural targets of the virus –– to soak up SARS-CoV-2 and keep it from infecting cells in a petri dish.

To gain entry, SARS-CoV-2 uses its spike protein to bind to two known proteins on human cells, called ACE2 and CD147. Blocking these interactions would keep the virus from infecting cells, so many researchers are trying to identify drugs directed against the spike protein. Anthony Griffiths, Liangfang Zhang and colleagues had a different idea: making a nanoparticle decoy with the virus’ natural targets, including ACE2 and CD147, to lure SARS-CoV-2 away from cells. And to test this idea, they conducted experiments with the actual SARS-CoV-2 virus in a biosafety level 4 lab.

The researchers coated a nanoparticle polymer core with cell membranes from either human lung epithelial cells or macrophages –– two cell types infected by SARS-CoV-2. They showed that the nanosponges had ACE2 and CD147, as well as other cell membrane proteins, projecting outward from the polymer core. When administered to mice, the nanosponges did not show any short-term toxicity. Then, the researchers treated cells in a dish with SARS-CoV-2 and the lung epithelial or macrophage nanosponges. Both decoys neutralized SARS-CoV-2 and prevented it from infecting cells to a similar extent. The researchers plan to next test the nanosponges in animals before moving to human clinical trials. In theory, the nanosponge approach would work even if SARS-CoV-2 mutates to resist other therapies, and it could be used against other viruses, as well, the researchers say.

In this illustration, a nanosponge coated with a human cell membrane acts as a decoy to prevent a virus from entering cells. Credit: Adapted from Nano Letters 2020, DOI: 10.1021/acs.nanolett.0c02278

There are two research teams involved, one at Boston University and the other at the University of California at San Diego (UC San Diego or UCSD). The June 18, 2020 Boston University news release (also on EurekAlert) by Kat J. McAlpine adds more details about the research, provides some insights from the researchers, and is a little redundant if you’ve already seen the ACS news release,

Imagine if scientists could stop the coronavirus infection in its tracks simply by diverting its attention away from living lung cells? A new therapeutic countermeasure, announced in a Nano Letters study by researchers from Boston University’s National Emerging Infectious Diseases Laboratories (NEIDL) and the University of California San Diego, appears to do just that in experiments that were carried out at the NEIDL in Boston.

The breakthrough technology could have major implications for fighting the SARS-CoV-2 virus responsible for the global pandemic that’s already claimed nearly 450,000 lives and infected more than 8 million people. But, perhaps even more significantly, it has the potential to be adapted to combat virtually any virus, such as influenza or even Ebola.

“I was skeptical at the beginning because it seemed too good to be true,” says NEIDL microbiologist Anna Honko, one of the co-first authors on the study. “But when I saw the first set of results in the lab, I was just astonished.”

The technology consists of very small, nanosized drops of polymers–essentially, soft biofriendly plastics–covered in fragments of living lung cell and immune cell membranes.

“It looks like a nanoparticle coated in pieces of cell membrane,” Honko says. “The small polymer [droplet] mimics a cell having a membrane around it.”

The SARS-CoV-2 virus seeks out unique signatures of lung cell membranes and latches onto them. When that happens inside the human body, the coronavirus infection takes hold, with the SARS-CoV-2 viruses hijacking lung cells to replicate their own genetic material. But in experiments at the NEIDL, BU researchers observed that polymer droplets laden with pieces of lung cell membrane did a better job of attracting the SARS-CoV-2 virus than living lung cells. [emphasis mine]

By fusing with the SARS-CoV-2 virus better than living cells can, the nanotechnology appears to be an effective countermeasure to coronavirus infection, preventing SARS-CoV-2 from attacking cells.

“Our guess is that it acts like a decoy, it competes with cells for the virus,” says NEIDL microbiologist Anthony Griffiths, co-corresponding author on the study. “They are little bits of plastic, just containing the outer pieces of cells with none of the internal cellular machinery contained inside living cells. Conceptually, it’s such a simple idea. It mops up the virus like a sponge.”

That attribute is why the UC San Diego and BU research team call the technology “nanosponges.” Once SARS-CoV-2 binds with the cell fragments inside a nanosponge droplet–each one a thousand times smaller than the width of a human hair–the coronavirus dies. Although the initial results are based on experiments conducted in cell culture dishes, the researchers believe that inside a human body, the biodegradable nanosponges and the SARS-CoV-2 virus trapped inside them could then be disposed of by the body’s immune system. The immune system routinely breaks down and gets rid of dead cell fragments caused by infection or normal cell life cycles.

There is also another important effect that the nanosponges have in the context of coronavirus infection. Honko says nanosponges containing fragments of immune cells can soak up cellular signals that increase inflammation [emphases mine]. Acute respiratory distress, caused by an inflammatory cascade inside the lungs, is the most deadly aspect of the coronavirus infection, sending patients into the intensive care unit for oxygen or ventilator support to help them breathe.

But the nanosponges, which can attract the inflammatory molecules that send the immune system into dangerous overdrive, can help tamp down that response, Honko says. By using both kinds of nanosponges, some containing lung cell fragments and some containing pieces of immune cells, she says it’s possible to “attack the coronavirus and the [body’s] response” responsible for disease and eventual lung failure.

At the NEIDL, Honko and Griffiths are now planning additional experiments to see how well the nanosponges can prevent coronavirus infection in animal models of the disease. They plan to work closely with the team of engineers at UC San Diego, who first developed the nanosponges more than a decade ago, to tailor the technology for eventual safe and effective use in humans.

“Traditionally, drug developers for infectious diseases dive deep on the details of the pathogen in order to find druggable targets,” said Liangfang Zhang, a UC San Diego nanoengineer and leader of the California-based team, according to a UC San Diego press release. “Our approach is different. We only need to know what the target cells are. And then we aim to protect the targets by creating biomimetic decoys.”

When the novel coronavirus first appeared, the idea of using the nanosponges to combat the infection came to Zhang almost immediately. He reached out to the NEIDL for help. Looking ahead, the BU and UC San Diego collaborators believe the nanosponges can easily be converted into a noninvasive treatment.

“We should be able to drop it right into the nose,” Griffiths says. “In humans, it could be something like a nasal spray.”

Honko agrees: “That would be an easy and safe administration method that should target the appropriate [respiratory] tissues. And if you wanted to treat patients that are already intubated, you could deliver it straight into the lung.”

Griffiths and Honko are especially intrigued by the nanosponges as a new platform for treating all types of viral infections. “The broad spectrum aspect of this is exceptionally appealing,” Griffiths says. The researchers say the nanosponge could be easily adapted to house other types of cell membranes preferred by other viruses, creating many new opportunities to use the technology against other tough-to-treat infections like the flu and even deadly hemorrhagic fevers caused by Ebola, Marburg, or Lassa viruses.

“I’m interested in seeing how far we can push this technology,” Honko says.

The University of California as San Diego has released a video illustrating the nanosponges work,

There’s also this June 17, 2020 University of California at San Diego (UC San Diego) news release (also on EurekAlert) by Ioana Patringenaru, which offers extensive new detail along with, if you’ve read one or both of the news releases in the above, a few redundant bits,

Nanoparticles cloaked in human lung cell membranes and human immune cell membranes can attract and neutralize the SARS-CoV-2 virus in cell culture, causing the virus to lose its ability to hijack host cells and reproduce.

The first data describing this new direction for fighting COVID-19 were published on June 17 in the journal Nano Letters. The “nanosponges” were developed by engineers at the University of California San Diego and tested by researchers at Boston University.

The UC San Diego researchers call their nano-scale particles “nanosponges” because they soak up harmful pathogens and toxins.

In lab experiments, both the lung cell and immune cell types of nanosponges caused the SARS-CoV-2 virus to lose nearly 90% of its “viral infectivity” in a dose-dependent manner. Viral infectivity is a measure of the ability of the virus to enter the host cell and exploit its resources to replicate and produce additional infectious viral particles.

Instead of targeting the virus itself, these nanosponges are designed to protect the healthy cells the virus invades.

“Traditionally, drug developers for infectious diseases dive deep on the details of the pathogen in order to find druggable targets. Our approach is different. We only need to know what the target cells are. And then we aim to protect the targets by creating biomimetic decoys,” said Liangfang Zhang, a nanoengineering professor at the UC San Diego Jacobs School of Engineering.

His lab first created this biomimetic nanosponge platform more than a decade ago and has been developing it for a wide range of applications ever since [emphasis mine]. When the novel coronavirus appeared, the idea of using the nanosponge platform to fight it came to Zhang “almost immediately,” he said.

In addition to the encouraging data on neutralizing the virus in cell culture, the researchers note that nanosponges cloaked with fragments of the outer membranes of macrophages could have an added benefit: soaking up inflammatory cytokine proteins, which are implicated in some of the most dangerous aspects of COVID-19 and are driven by immune response to the infection.

Making and testing COVID-19 nanosponges

Each COVID-19 nanosponge–a thousand times smaller than the width of a human hair–consists of a polymer core coated in cell membranes extracted from either lung epithelial type II cells or macrophage cells. The membranes cover the sponges with all the same protein receptors as the cells they impersonate–and this inherently includes whatever receptors SARS-CoV-2 uses to enter cells in the body.

The researchers prepared several different concentrations of nanosponges in solution to test against the novel coronavirus. To test the ability of the nanosponges to block SARS-CoV-2 infectivity, the UC San Diego researchers turned to a team at Boston University’s National Emerging Infectious Diseases Laboratories (NEIDL) to perform independent tests. In this BSL-4 lab–the highest biosafety level for a research facility–the researchers, led by Anthony Griffiths, associate professor of microbiology at Boston University School of Medicine, tested the ability of various concentrations of each nanosponge type to reduce the infectivity of live SARS-CoV-2 virus–the same strains that are being tested in other COVID-19 therapeutic and vaccine research.

At a concentration of 5 milligrams per milliliter, the lung cell membrane-cloaked sponges inhibited 93% of the viral infectivity of SARS-CoV-2. The macrophage-cloaked sponges inhibited 88% of the viral infectivity of SARS-CoV-2. Viral infectivity is a measure of the ability of the virus to enter the host cell and exploit its resources to replicate and produce additional infectious viral particles.

“From the perspective of an immunologist and virologist, the nanosponge platform was immediately appealing as a potential antiviral because of its ability to work against viruses of any kind. This means that as opposed to a drug or antibody that might very specifically block SARS-CoV-2 infection or replication, these cell membrane nanosponges might function in a more holistic manner in treating a broad spectrum of viral infectious diseases. I was optimistically skeptical initially that it would work, and then thrilled once I saw the results and it sunk in what this could mean for therapeutic development as a whole,” said Anna Honko, a co-first author on the paper and a Research Associate Professor, Microbiology at Boston University’s National Emerging Infectious Diseases Laboratories (NEIDL).

In the next few months, the UC San Diego researchers and collaborators will evaluate the nanosponges’ efficacy in animal models. The UC San Diego team has already shown short-term safety in the respiratory tracts and lungs of mice. If and when these COVID-19 nanosponges will be tested in humans depends on a variety of factors, but the researchers are moving as fast as possible.

“Another interesting aspect of our approach is that even as SARS-CoV-2 mutates, as long as the virus can still invade the cells we are mimicking, our nanosponge approach should still work. I’m not sure this can be said for some of the vaccines and therapeutics that are currently being developed,” said Zhang.

The researchers also expect these nanosponges would work against any new coronavirus or even other respiratory viruses, including whatever virus might trigger the next respiratory pandemic.

Mimicking lung epithelial cells and immune cells

Since the novel coronavirus often infects lung epithelial cells as the first step in COVID-19 infection, Zhang and his colleagues reasoned that it would make sense to cloak a nanoparticle in fragments of the outer membranes of lung epithelial cells to see if the virus could be tricked into latching on it instead of a lung cell.

Macrophages, which are white blood cells that play a major role in inflammation, also are very active in the lung during the course of a COVID-19 illness, so Zhang and colleagues created a second sponge cloaked in macrophage membrane.

The research team plans to study whether the macrophage sponges also have the ability to quiet cytokine storms in COVID-19 patients.

“We will see if the macrophage nanosponges can neutralize the excessive amount of these cytokines as well as neutralize the virus,” said Zhang.

Using macrophage cell fragments as cloaks builds on years of work to develop therapies for sepsis using macrophage nanosponges.

In a paper published in 2017 in Proceedings of the National Academy of Sciences, Zhang and a team of researchers at UC San Diego showed that macrophage nanosponges can safely neutralize both endotoxins and pro-inflammatory cytokines in the bloodstream of mice. A San Diego biotechnology company co-founded by Zhang called Cellics Therapeutics is working to translate this macrophage nanosponge work into the clinic.

A potential COVID-19 therapeutic The COVID-19 nanosponge platform has significant testing ahead of it before scientists know whether it would be a safe and effective therapy against the virus in humans, Zhang cautioned [emphasis mine]. But if the sponges reach the clinical trial stage, there are multiple potential ways of delivering the therapy that include direct delivery into the lung for intubated patients, via an inhaler like for asthmatic patients, or intravenously, especially to treat the complication of cytokine storm.

A therapeutic dose of nanosponges might flood the lung with a trillion or more tiny nanosponges that could draw the virus away from healthy cells. Once the virus binds with a sponge, “it loses its viability and is not infective anymore, and will be taken up by our own immune cells and digested,” said Zhang.

“I see potential for a preventive treatment, for a therapeutic that could be given early because once the nanosponges get in the lung, they can stay in the lung for some time,” Zhang said. “If a virus comes, it could be blocked if there are nanosponges waiting for it.”

Growing momentum for nanosponges

Zhang’s lab at UC San Diego created the first membrane-cloaked nanoparticles over a decade ago. The first of these nanosponges were cloaked with fragments of red blood cell membranes. These nanosponges are being developed to treat bacterial pneumonia and have undergone all stages of pre-clinical testing by Cellics Therapeutics, the San Diego startup cofounded by Zhang. The company is currently in the process of submitting the investigational new drug (IND) application to the FDA for their lead candidate: red blood cell nanosponges for the treatment of methicillin-resistant staphylococcus aureus (MRSA) pneumonia. The company estimates the first patients in a clinical trial will be dosed next year.

The UC San Diego researchers have also shown that nanosponges can deliver drugs to a wound site; sop up bacterial toxins that trigger sepsis; and intercept HIV before it can infect human T cells.

The basic construction for each of these nanosponges is the same: a biodegradable, FDA-approved polymer core is coated in a specific type of cell membrane, so that it might be disguised as a red blood cell, or an immune T cell or a platelet cell. The cloaking keeps the immune system from spotting and attacking the particles as dangerous invaders.

“I think of the cell membrane fragments as the active ingredients. This is a different way of looking at drug development,” said Zhang. “For COVID-19, I hope other teams come up with safe and effective therapies and vaccines as soon as possible. At the same time, we are working and planning as if the world is counting on us.”

I wish the researchers good luck. For the curious, here’s a link to and a citation for the paper,

Cellular Nanosponges Inhibit SARS-CoV-2 Infectivity by Qiangzhe Zhang, Anna Honko, Jiarong Zhou, Hua Gong, Sierra N. Downs, Jhonatan Henao Vasquez, Ronnie H. Fang, Weiwei Gao, Anthony Griffiths, and Liangfang Zhang. Nano Lett. 2020, XXXX, XXX, XXX-XXX DOI: https://doi.org/10.1021/acs.nanolett.0c02278 Publication Date:June 17, 2020 Copyright © 2020 American Chemical Society

This paper appears to be open access.

Here, too, is the Cellics Therapeutics website.

Brain scan variations

The Scientist is a magazine I do not feature here often enough. The latest issue (June 2020) features a May 20, 2020 opinion piece by Ruth Williams on a recent study about interpretating brain scans—70 different teams of neuroimaging experts were involved (Note: Links have been removed),

In a test of scientific reproducibility, multiple teams of neuroimaging experts from across the globe were asked to independently analyze and interpret the same functional magnetic resonance imaging dataset. The results of the test, published in Nature today (May 20), show that each team performed the analysis in a subtly different manner and that their conclusions varied as a result. While highlighting the cause of the irreproducibility—human methodological decisions—the paper also reveals ways to safeguard future studies against it.

Problems with reproducibility plague all areas of science, and have been particularly highlighted in the fields of psychology and cancer through projects run in part by the Center for Open Science. Now, neuroimaging has come under the spotlight thanks to a collaborative project by neuroimaging experts around the world called the Neuroimaging Analysis Replication and Prediction Study (NARPS).

Neuroimaging, specifically functional magnetic resonance imaging (fMRI), which produces pictures of blood flow patterns in the brain that are thought to relate to neuronal activity, has been criticized in the past for problems such as poor study design and statistical methods, and specifying hypotheses after results are known (SHARKing), says neurologist Alain Dagher of McGill University who was not involved in the study. A particularly memorable criticism of the technique was a paper demonstrating that, without needed statistical corrections, it could identify apparent brain activity in a dead fish.

Perhaps because of such criticisms, nowadays fMRI “is a field that is known to have a lot of cautiousness about statistics and . . . about the sample sizes,” says neuroscientist Tom Schonberg of Tel Aviv University, an author of the paper and co-coordinator of NARPS. Also, unlike in many areas of biology, he adds, the image analysis is computational, not manual, so fewer biases might be expected to creep in.

Schonberg was therefore a little surprised to see the NARPS results, admitting, “it wasn’t easy seeing this variability, but it was what it was.”

The study, led by Schonberg together with psychologist Russell Poldrack of Stanford University and neuroimaging statistician Thomas Nichols of the University of Oxford, recruited independent teams of researchers around the globe to analyze and interpret the same raw neuroimaging data—brain scans of 108 healthy adults taken while the subjects were at rest and while they performed a simple decision-making task about whether to gamble a sum of money.

Each of the 70 research teams taking part used one of three different image analysis software packages. But variations in the final results didn’t depend on these software choices, says Nichols. Instead, they came down to numerous steps in the analysis that each require a human’s decision, such as how to correct for motion of the subjects’ heads, how signal-to-noise ratios are enhanced, how much image smoothing to apply—that is, how strictly the anatomical regions of the brain are defined—and which statistical approaches and thresholds to use.

If this topic interests you, I strongly suggest you read Williams’ article in its entirety.

Here are two links to the paper,

Variability in the analysis of a single neuroimaging dataset by many teams. Nature DOI: https://doi.org/10.1038/s41586-020-2314-9 Published online: 20 May 2020 Check for updates

This first one seems to be a free version of the paper.

Variability in the analysis of a single neuroimaging dataset by many teams by R. Botvinik-Nezer, F. Holzmeister, C. F. Camerer, et al. (at least 70 authors in total) Nature 582, 84–88 (2020). DOI: https://doi.org/10.1038/s41586-020-2314-9 Published 20 May 2020 Issue Date 04 June 2020

This version is behind a paywall.

Gold nanoparticles could help detect the presence of COVID-19 in ten minutes

If this works out, it would make testing for COVID-19 an infinitely easier task. From a May 29, 2020 news item on phys.org,

Scientists from the University of Maryland School of Medicine (UMSOM) developed an experimental diagnostic test for COVID-19 that can visually detect the presence of the virus in 10 minutes. It uses a simple assay containing plasmonic gold nanoparticles to detect a color change when the virus is present. The test does not require the use of any advanced laboratory techniques, such as those commonly used to amplify DNA, for analysis. The authors published their work last week [May 21, 2020] in the American Chemical Society’s nanotechnology journal ACS Nano.

“Based on our preliminary results, we believe this promising new test may detect RNA [ribonucleic acid] material from the virus as early as the first day of infection. Additional studies are needed, however, to confirm whether this is indeed the case,” said study leader Dipanjan Pan, PhD, Professor of Diagnostic Radiology and Nuclear Medicine and Pediatrics at the UMSOM.

Caption: A nasal swab containing a test sample is mixed with a simple lab test. It contains a liquid mixed with gold nanoparticles attached to a molecule that binds to the novel coronavirus. If the virus is present, the gold nanoparticles turns the solution a deep blue color (bottom of the tube) and a precipitation is noticed. If it is not present, the solution retains its original purple color. Credit: University of Maryland School of Medicine

A May 28, 2020 University of Maryland news release (also on EurekAlert), which originated the news item, provides more detail,

Once a nasal swab or saliva sample is obtained from a patient, the RNA is extracted from the sample via a simple process that takes about 10 minutes. The test uses a highly specific molecule attached to the gold nanoparticles to detect a particular protein. This protein is part of the genetic sequence that is unique to the novel coronavirus. When the biosensor binds to the virus’s gene sequence, the gold nanoparticles respond by turning the liquid reagent from purple to blue.

“The accuracy of any COVID-19 test is based on being able to reliably detect any virus. This means it does not give a false negative result if the virus actually is present, nor a false positive result if the virus is not present,” said Dr. Pan. “Many of the diagnostic tests currently on the market cannot detect the virus until several days after infection. For this reason, they have a significant rate of false negative results.”

Dr. Pan created a company called VitruVian Bio to develop the test for commercial application. He plans to have a pre-submission meeting with the U.S. Food and Drug Administration (FDA) within the next month to discuss requirements for getting an emergency use authorization for the test. New FDA policy allows for the marketing of COVID-19 tests without requiring them to go through the usual approval or clearance process. These tests do, however, need to meet certain validation testing requirements to ensure that they provide reliable results.

“This RNA-based test appears to be very promising in terms of detecting the virus. The innovative approach provides results without the need for a sophisticated laboratory facility,” said study co-author Matthew Frieman, PhD, Associate Professor of Microbiology and Immunology at UMSOM.

Although more clinical studies are warranted, this test could be far less expensive to produce and process than a standard COVID-19 lab test; it does not require laboratory equipment or trained personnel to run the test and analyze the results. If this new test meets FDA expectations, it could potentially be used in daycare centers, nursing homes, college campuses, and work places as a surveillance technique to monitor any resurgence of infections.

In Dr. Pan’s laboratory, research scientist Parikshit Moitra, PhD, and UMSOM research fellow Maha Alafeef conducted the studies along with research fellow Ketan Dighe from UMBC.

Dr. Pan holds a joint appointment with the College of Engineering at the University of Maryland Baltimore County and is also a faculty member of the Center for Blood Oxygen Transport and Hemostasis (CBOTH).

“This is another example of how our faculty is driving innovation to fulfill a vital need to expand the capacity of COVID-19 testing,” said Dean E. Albert Reece, MD, PhD, MBA, who is also Executive Vice President for Medical Affairs, UM Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor, University of Maryland School of Medicine. “Our nation will be relying on inexpensive, rapid tests that can be dispersed widely and used often until we have effective vaccines against this pandemic.”

Here’s a link to and a citation for the paper,

Selective Naked-Eye Detection of SARS-CoV-2 Mediated by N Gene Targeted Antisense Oligonucleotide Capped Plasmonic Nanoparticles by Parikshit Moitra, Maha Alafeef, Ketan Dighe, Matthew B. Frieman, and Dipanjan Pan. ACS Nano 2020, XXXX, XXX, XXX-XXX DOI: https://doi.org/10.1021/acsnano.0c03822 Publication Date:May 21, 2020 Copyright © 2020 American Chemical Society

This paper appears to be open access.

I tried to find Dr. Pan’s company, VitruVian Bio and found a business with an almost identical name, Vitruvian Biomedical, which does not include Dr. Pan on its management team list and this company’s focus is on Alzheimer’s Disease. Finally, there is no mention of the COVID-19 test anywhere on the Vitruvian Biomedical website.