Is Nanotechnology helping in the fight against Covid 19, or Cancer?

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Re: Is Nanotechnology helping in the fight against Covid 19, or Cancer?

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Micro-environmental influences on artificial micromotors

3/31/21

https://phys.org/news/2021-03-micro-env ... otors.html


By harvesting energy from their surrounding environments, particles named 'artificial micromotors' can propel themselves in specific directions when placed in aqueous solutions. In current research, a popular choice of micromotor is the spherical 'Janus particle' - featuring two distinct sides with different physical properties. Until now, however, few studies have explored how these particles interact with other objects in their surrounding microenvironments. In an experiment detailed in EPJ E, researchers in Germany and The Netherlands, led by Larysa Baraban at Helmholtz-Zentrum Dresden-Rossendorf, show for the first time how the velocities of Janus particles relate to the physical properties of nearby barriers.

The team's discoveries could help researchers to engineer micromotors which can traverse highly complex biological environments. These particles would prove invaluable for cutting-edge medical techniques including drug delivery and nano-surgery. In their study, Baraban and colleagues prepared two types of Janus sphere: the first one with a negatively charged surface, the second, with a positive charged coating. When placed in deionized water, both types generated an ion concentration gradient, and propelled themselves in opposite directions. Nearby, the researchers also placed a glass substrate carrying a variety of charge densities. When both substrate and particle coating had alike charges, the negative particles propelled themselves away from the surface at varying velocities.

For positively-charged substrates and particle coatings, Baraban's team found that these speeds showed a positive correlation with the substrate's charge density. According to the researchers, this behavior arose since chemical reactions on the positively-charged coatings created their own ion concentration gradients in the surrounding fluid. This generated 'osmotic' flows along the charged substrate, causing the Janus particle to speed up. The discovery is a crucial step forward in our understanding of how self-propelled particles are influenced by the surrounding microenvironment. With further research, this could soon enable researchers to engineer Janus particles with specific speeds and directions, making them better suited to navigating complex environments.

More information: Tao Huang et al, Impact of surface charge on the motion of light-activated Janus micromotors, The European Physical Journal E (2021). DOI: 10.1140/epje/s10189-021-00008-x
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Re: Is Nanotechnology helping in the fight against Covid 19, or Cancer?

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New nanosensor holds promise for diagnosing, treating neurological disease

4/13/21


https://phys.org/news/2021-04-nanosenso ... sease.html


Every movement in the human body—from lifting our arms to our beating hearts—is regulated in some way by signals from our brains. Until recently, scientists often tracked and understood that brain-body communication only after the fact, sort of like listening to a voicemail as opposed to being on a call.

But researchers at Northeastern have developed a new type of nanosensor that allows scientists to image communication between the brain and the body in real time. They now can listen in on the call.

Heather Clark, professor of bioengineering and chemistry at Northeastern, and James Monaghan, associate professor of biology, along with colleagues at Northeastern and researchers from the University of California, San Francisco, developed a DNA-based nanosensor that detects a specific neurotransmitter, acetylcholine, as it's released and picked up by target cells in living animals. They published their findings in the journal Proceedings of the National Academy of Sciences this month.

"It's critical, in terms of understanding the relationship between the brain and the body, to understand when the nerves are communicating—when they're firing signals to tell the heart rate to speed up or slow down, for example," Monaghan says.

Understanding this communication is particularly important when there's a breakdown. Illnesses such as Parkinson's Disease are the result of the degeneration of nerve cells and the breakdown of communication between the brain and the body.

A burgeoning field of medicine known as bioelectronic medicine seeks to use highly specific nerve stimulation to treat neurological diseases. In order to precisely target the nerves, scientists need to know how they react in real time and in living organisms—Clark and Monaghan's nanosensor represents a step in that direction.

"If you're going to use nerve stimulation as a medicine, you need a readout of how much stimulus you provided," Monaghan says. "Dr. Clark's chemistry and innovation in this area of sensor development would provide that readout for the neurotransmitter acetylcholine."

The nanosensor consists of a fluorescent component that glows in the presence of acetylcholine and can be seen in living mice, in real time. It's kind of like seeing someone's cell phone light up for a phone call, but on a molecular level.

Existing tools such as microelectrodes and microdialysis enable scientists to detect acetylcholine in the central nervous system but fall short when it comes to the peripheral nervous system, which is everything outside the brain and spinal cord.

Clark, Monaghan, and their colleagues utilized powerful microscopes housed at Northeastern, to watch the fluorescent markers light up as the neurotransmitter was activated in their experiments.

The development of this nanosensor is just the beginning, though, and the researchers hope to create even hardier sensors in the future.

Clark and Monaghan also expect that the sophisticated imaging tools they used to develop this nanosensor will be used by other scientists at Northeastern and beyond. They head the Institute for the Chemical Imaging of Living Systems, a new organization at the university in which researchers can take advantage of five state-of-the-art microscopes located in the Interdisciplinary Science and Engineering Complex.

"This is a set of tools that researchers can use to answer fundamental questions about biochemical signaling in the body," Clark says. "As a scientist, I love developing new tools and fostering the kind of interdisciplinary research that could have a real impact in the world."
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Re: Is Nanotechnology helping in the fight against Covid 19, or Cancer?

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Superbug killer: New nanotech destroys bacteria and fungal cells

4/13/21


https://phys.org/news/2021-04-superbug- ... ungal.html


Researchers have developed a new superbug-destroying coating that could be used on wound dressings and implants to prevent and treat potentially deadly bacterial and fungal infections.

The material is one of the thinnest antimicrobial coatings developed to date and is effective against a broad range of drug-resistant bacteria and fungal cells, while leaving human cells unharmed.

Antibiotic resistance is a major global health threat, causing at least 700,000 deaths a year. Without the development of new antibacterial therapies, the death toll could rise to 10 million people a year by 2050, equating to $US100 trillion in health care costs.

While the health burden of fungal infections is less recognized, globally they kill about 1.5 million people each year and the death toll is growing. An emerging threat to hospitalized COVID-19 patients for example is the common fungus, Aspergillus, which can cause deadly secondary infections.

The new coating from a team led by RMIT University is based on an ultra-thin 2D material that until now has mainly been of interest for next-generation electronics.

Studies on black phosphorus (BP) have indicated it has some antibacterial and antifungal properties, but the material has never been methodically examined for potential clinical use.

The new research, published in the American Chemical Society's journal Applied Materials & Interfaces, reveals that BP is effective at killing microbes when spread in nanothin layers on surfaces like titanium and cotton, used to make implants and wound dressings.

Co-lead researcher Dr. Aaron Elbourne said finding one material that could prevent both bacterial and fungal infections was a significant advance.

"These pathogens are responsible for massive health burdens and as drug-resistance continues to grow, our ability to treat these infections becomes increasingly difficult," Elbourne, a Postdoctoral Fellow in the School of Science at RMIT, said.

"We need smart new weapons for the war on superbugs, which don't contribute to the problem of antimicrobial resistance.

"Our nanothin coating is a dual bug killer that works by tearing bacteria and fungal cells apart, something microbes will struggle to adapt to. It would take millions of years to naturally evolve new defenses to such a lethal physical attack.

"While we need further research to be able to apply this technology in clinical settings, it's an exciting new direction in the search for more effective ways to tackle this serious health challenge."

Co-lead researcher Associate Professor Sumeet Walia, from RMIT's School of Engineering, has previously led groundbreaking studies using BP for artificial intelligence technology and brain-mimicking electronics.

"BP breaks down in the presence of oxygen, which is normally a huge problem for electronics and something we had to overcome with painstaking precision engineering to develop our technologies," Walia said.

"But it turns out materials that degrade easily with oxygen can be ideal for killing microbes—it's exactly what the scientists working on antimicrobial technologies were looking for.

"So our problem was their solution."

How the nanothin bug killer works

As BP breaks down, it oxidizes the surface of bacteria and fungal cells. This process, known as cellular oxidization, ultimately works to rip them apart.

In the new study, first author and Ph.D. researcher Zo Shaw tested the effectiveness of nanothin layers of BP against five common bacteria strains, including E. coli and drug-resistant MRSA, as well as five types of fungus, including Candida auris.

In just two hours, up to 99% of bacterial and fungal cells were destroyed.

Importantly, the BP also began to self-degrade in that time and was entirely disintegrated within 24 hours—an important feature that shows the material would not accumulate in the body.

The laboratory study identified the optimum levels of BP that have a deadly antimicrobial effect while leaving human cells healthy and whole.

The researchers have now begun experimenting with different formulations to test the efficacy on a range of medically-relevant surfaces.

The team is keen to collaborate with potential industry partners to further develop the technology, for which a provisional patent application has been filed.
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Re: Is Nanotechnology helping in the fight against Covid 19, or Cancer?

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Respiratory viral pathogens like SARS-CoV-2 easy to test on-site with new nanofilm

4/15/21


https://phys.org/news/2021-04-respirato ... -easy.html


Researchers in South Korea have developed a plasmonic isothermal recombinase polymerase amplification (RPA) array chip. This first plasmoinc isothermal PCR technology can detect eight types of pathogens (four bacteria and four viruses) that cause acute respiratory infectious diseases; the analysis takes only 30 minutes. The research was led by Dr. Sung-Gyu Park and Dr. Ho Sang Jung of the Korea Institute of Materials Science (KIMS, President Jung-Hwan Lee) and by Dr. Min-Young Lee and Dr. Ayoung Woo of Samsung Medical Center.

The current detection technology for COVID-19 is impossible to use on-site, as results take about four hours or more after specimen collection, making it difficult to isolate the patient quickly.

To solve this problem, the researchers combined isothermal PCR technology with a 3D Au-nanostructured substrate that can amplify the fluorescence signal of RPA products with DNA amplicons and sucessfully detect bacterial DNA and viral RNA within 30 minutes.

In addition, the research team also developed a 3D plasmonic array chip for multiplex molecular detections. This is a chip that can simultaneously analyze eight pathogens (four bacteria and four viruses).

This multiplex diagnosis technology is also applicable to nasopharyngeal swabs. The team is planning to perform the reliability test of medical devices through large-scale clinical trials on COVID-19 patients and is applying for approval from the Ministry of Food and Drug Safety.

"We developed a medical device that can detect pathogens in half an hour on-site, by developing core plasmonic nanomaterials that enable ultra-sensitive pathogene diagnosis of more than 10 types of respiratory viral pathogens. The on-site molecular diagnostic devices can be deployed rapidly as we actively research with Samsung Medical Center and domestic diagnostic device companies," said Dr. Sung-Gyu Park, a principal research scientist of KIMS.

More information: Ayoung Woo et al, Rapid and sensitive multiplex molecular diagnosis of respiratory pathogens using plasmonic isothermal RPA array chip, Biosensors and Bioelectronics (2021). DOI: 10.1016/j.bios.2021.113167
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Re: Is Nanotechnology helping in the fight against Covid 19, or Cancer?

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Research finds a potential new 'silver bullet' nanoparticle to treat brain cancer

4/16/21


https://phys.org/news/2021-04-potential ... brain.html


ANSTO has contributed to a comprehensive investigation of a promising type of nanoparticle that could potentially be used for intractable brain cancers in a combined therapy.

The study, which was led by Dr. Moeava Tehei and researchers from the University of Wollongong in combination with clinical partners, characterized and evaluated the properties of nanoparticles made from lanthanum manganite, that were doped with silver atoms.

The investigators found that the nanoparticles had potential clinical application for their synergistic effects to be used in combination with radiation treatment, hyperthermia (using heat to kill cancer cells) and their intrinsic toxicity to cancer cells.

The research was published in Materials Science & Engineering C.

Nanoparticles are small enough to cross the blood brain barrier that prohibits other therapies.

In addition to a wide variety of other methods of analysis, studies of the magnetic properties were undertaken at ANSTO.

The magnetic properties were important because they could be used to get the nanoparticles to the target cancer site and in magnetic hyperthermia treatment.

Dr. Kirrily Rule, a co-author on the paper, supervised investigations of magnetic and chemical changes to nanoparticles of silver-doped lanthanum manganite at two temperatures on the high-resolution powder diffractometer Echidna at ANSTO's Australian Centre for Neutron Scattering.

Although an expert in the magnetic behavior of low-dimensional materials with quantum properties, Rule said she was excited by the opportunity to change focus and assist in medical physics-related research.

The magnetic behavior of the nanoparticles at two temperatures was important to the study because the magnetic properties of the silver-doped nanoparticles change at different transition temperatures.

The magnetism measurements on Echidna were performed at 10 degrees Kelvin and 300 Kelvin.

At about 300 degrees Kelvin, close to body-temperature, the magnetic ordering stops.

"There is a critical temperature region for hyperthermia treatment," said Rule.

The magnetisation results indicated that the nanomaterial was more likely to order ferromagnetically, and that the ordering temperature when the magnetic moments aligned, was higher for a higher percentage of silver.

"So, it appears that the silver was responsible for the higher transition temperatures of these nanoparticles," said Rule.

The most promising sample for hyperthermia and cancer toxicity was lanthanum manganite that was doped with a 10 percent concentration of silver, as it retained a level of ferromagnetism at 300 degrees Kelvin.

However, Dr. Tehei said that the 5 percent doping may turn out to be the most interesting when combined with radiation because of its selectivity and cancer toxicity.

This suggested to the investigators that the temperature range for hyperthermia treatments could be manipulated by modifying the doping percentage.

Importantly, the biological effects of the nanoparticles and doped nanoparticles were toxic to cancer cells but not the normal cells.

The research helped elucidate how the doped nanoparticles were killing cancer cells by producing high levels of reactive oxidative stress.

More information: Abass Khochaiche et al. First extensive study of silver-doped lanthanum manganite nanoparticles for inducing selective chemotherapy and radio-toxicity enhancement, Materials Science and Engineering: C (2021). DOI: 10.1016/j.msec.2021.111970
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Re: Is Nanotechnology helping in the fight against Covid 19, or Cancer?

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What is the role of nanotechnology in the current COVID-19 outbreak?

4/27/21

https://www.news-medical.net/news/20210 ... break.aspx


The nanotechnology-based medicine platforms against coronavirus disease 2019 (COVID-19) bears hope for relief from the pandemic to save lives and mitigate the infection as part of a broader global public health agenda.

In a recent review article, an interdisciplinary research team discussed the potential of nanoparticles (NPs) as a drug itself or as a platform for the aim of drug and vaccine repurposing and development. They also looked at advanced detection strategies based on nanotechnology. Scientists are encouraged to design effective and cost-effective nanoplatforms for the prevention, diagnosis, and treatment of infectious diseases. The team has recently published their review in the journal Heliyon.

Over the last two decades, coronaviruses have become a serious epidemic problem with severe acute respiratory syndrome coronavirus (SARS), the Middle East respiratory syndrome (MERS) and the current pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Because of its high transmission rate and high reproduction number, COVID-19 has resulted in deadly outcomes.

Since December 2019, SARS-CoV-2 infection has caused over 143.5 million cases and over 3 million deaths. Yet, effective therapeutic drugs for COVID-19 are still unavailable. Due to the urgent nature of the need for a remedial agent to tackle COVID-19, drug repurposing is a promising strategy.

To address the mitigation strategies against COVID-19, it is crucial to have a complete understanding of the virus, the host interaction and responses. Pathologically, it is known that the ACE2 (angiotensin-converting enzyme 2), a cell surface receptor in humans (over-expressed in the lung, heart, kidney, testis, intestine, and brain), is the main receptor of the SARS-CoV-2 virus. The viral receptor-binding domain (RBD) on the spike protein of the coronavirus binds to ACE2. Another receptor, CD147 (Basigin), as an extracellular matrix metalloproteinase inducer, is also considered to be a receptor for SARS-CoV-2 on the surface of cells, including epithelial cells, endothelial cells, leukocytes and red blood cells.

To design and evaluate successful drug or vaccine repurposing, the team first reviewed how similar SARS-CoV-2 is to other betacoronaviruses (the MERS-CoV and SARS-CoV) as a genotype and structure. The reviewers recommend drug repurposing based on the study of the information on the nucleotide sequence identity, sequence homology, similarity between proteins of the envelope, membrane, nucleocapsid, amino acid identities of the spike and RBD, mutations involving single amino acids, and function of every non-structural protein (nsp) and its sequence identity.

They conclude here that the drugs and vaccines can be selected based on those that share antiviral efficacy by the targeting of the envelope, membrane, nucleocapsid, S2 spike, RdRp (RNA dependent RNA polymerase), and helicase.

The reviewers note that accurate and early detection plays a critical role in limiting COVID-19 spread and prevents future epidemics. Nanotechnology, based on molecular techniques and specific pathogens targeting, may be very useful in this regard.

New nanotechnologies involve colloidal gold NPs to detect antibodies, an ultrasensitive chiro-immunosensor for viruses based on chiral AuNPs (Au NPs)-quantum dot (QDs) nanocomposites, and RNA stabilization kit (for room temperature), and nanoplatforms (polymeric NPs, chaperone-mediated ferritin nanoparticles, nanobodies) for the diagnosis of coronaviruses. In this review article, the reviewers have tabulated the current nano-based approaches for viral diagnosis and treatment.

Further, they discussed the properties of NPs for the COVID-19 treatment: nanomedicine used in vectors, biosensors, drug and gene delivery. They highlighted the physicochemical characteristics and the physiological advantages of the ‘nano’ regime in the therapeutic area. Specifically, they discussed each drug, including a few nonspecific drugs, that are currently in use as anti-SARS-CoV-2 agents.

" The emergence of nanomaterials in recent years is swiftly transforming the scientific landscape of fields as diverse as aerospace, military, and medicine.”

The reviewers highlighted the role of the combination therapy and co-delivery systems such as the nanocarriers applied for the co-encapsulation of the candidate drugs such as remdesivir and hydroxychloroquine to treat COVID-19. Notably, they have presented the potential nano-based drugs that can be repurposed for the treatment of COVID-19.

Different types of carbon dots, gold nanorods (AuNRs), Fe2O3 NPs, nano-sponges, are investigated in pre-clinical assessments for COVID-19 therapy.

" Encapsulation of the hydroxychloroquine into the nanocarriers that deliver cargo to the respiratory system and decline systemic administration side effects such as retinopathy, myopathy, and heart diseases is valuable.”

Nanotechnology also plays a powerful role in vaccine development. The reviewers shared, “A promising strategy in vaccine development is taking benefits of mRNA owing to mimicking the natural infection and the ability to combine multiple mRNAs into a single vaccine that resulted in the stimulation of a more potent immune response.”

Importantly, the reviewers also pointed that, while there are some concerns about their toxicities, nano drugs can act as a double-edged sword. They are also a promising tool to enhance the efficacy of drugs to inhibit virus attachment, fusion, replication, and infection or even restrain the inflammatory and damaging cascade following virus infection in some patients.

In the present paper, the reviewers discussed the diagnostic and therapeutic strategies for the other viruses which have similar mechanisms of action with SARS-CoV-2. It is a comprehensive review extensively covering the current strategies in nanotechnology that may be repurposed to act against the COVID-19 pandemic.

Journal reference:

Shima Tavakol, Masoumeh Zahmatkeshan, Reza Mohammadinejad, Saeed Mehrzadi, Mohammad T. Joghataei, Mo S. Alavijeh, Alexander Seifalian. (2021) The role of nanotechnology in current COVID-19 outbreak. Heliyon. https://doi.org/10.1016/j.heliyon.2021.e06841, https://www.cell.com/heliyon/fulltext/S ... all%3Dtrue
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Re: Is Nanotechnology helping in the fight against Covid 19, or Cancer?

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Researchers design "nanotraps" to capture and destroy SARS-CoV-2 viruses

4/27/21


https://www.news-medical.net/news/20210 ... ruses.aspx


Researchers at the Pritzker School of Molecular Engineering (PME) at the University of Chicago have designed a completely novel potential treatment for COVID-19: nanoparticles that capture SARS-CoV-2 viruses within the body and then use the body's own immune system to destroy it.

These "Nanotraps" attract the virus by mimicking the target cells the virus infects. When the virus binds to the Nanotraps, the traps then sequester the virus from other cells and target it for destruction by the immune system.

In theory, these Nanotraps could also be used on variants of the virus, leading to a potential new way to inhibit the virus going forward. Though the therapy remains in early stages of testing, the researchers envision it could be administered via a nasal spray as a treatment for COVID-19.

The results were published April 19 in the journal Matter.

"Since the pandemic began, our research team has been developing this new way to treat COVID-19," said Asst. Prof. Jun Huang, whose lab led the research. "We have done rigorous testing to prove that these Nanotraps work, and we are excited about their potential."

Designing the perfect trap


To design the Nanotrap, the research team - led by postdoctoral scholar Min Chen and graduate student Jill Rosenberg - looked into the mechanism SARS-CoV-2 uses to bind to cells: a spike-like protein on its surface that binds to a human cell's ACE2 receptor protein.

To create a trap that would bind to the virus in the same way, they designed nanoparticles with a high density of ACE2 proteins on their surface. Similarly, they designed other nanoparticles with neutralizing antibodies on their surfaces. (These antibodies are created inside the body when someone is infected and are designed to latch onto the coronavirus in various ways).

Both ACE2 proteins and neutralizing antibodies have been used in treatments for COVID-19, but by attaching them to nanoparticles, the researchers created an even more robust system for trapping and eliminating the virus.

Made of FDA-approved polymers and phospholipids, the nanoparticles are about 500 nanometers in diameter - much smaller than a cell. That means the Nanotraps can reach more areas inside the body and more effectively trap the virus.

The researchers tested the safety of the system in a mouse model and found no toxicity. They then tested the Nanotraps against a pseudovirus - a less potent model of a virus that doesn't replicate - in human lung cells in tissue culture plates and found that they completely blocked entry into the cells.

Once the pseudovirus bound itself to the nanoparticle - which in tests took about 10 minutes after injection - the nanoparticles used a molecule that calls the body's macrophages to engulf and degrade the Nanotrap. Macrophages will generally eat nanoparticles within the body, but the Nanotrap molecule speeds up the process. The nanoparticles were cleared and degraded within 48 hours.

The researchers also tested the nanoparticles with a pseudovirus in an ex vivo lung perfusion system - a pair of donated lungs that is kept alive with a ventilator - and found that they completely blocked infection in the lungs.

They also collaborated with researchers at Argonne National Laboratory to test the Nanotraps with a live virus (rather than a pseudovirus) in an in vitro system. They found that their system inhibited the virus 10 times better than neutralizing antibodies or soluble ACE2 alone.
A potential future treatment for COVID-19 and beyond

Next the researchers hope to further test the system, including more tests with a live virus and on the many virus variants.

" That's what is so powerful about this Nanotrap. It's easily modulated. We can switch out different antibodies or proteins or target different immune cells, based on what we need with new variants."

- Jill Rosenberg, Graduate Student

The Nanotraps can be stored in a standard freezer and could ultimately be given via an intranasal spray, which would place them directly in the respiratory system and make them most effective.

The researchers say it is also possible to serve as a vaccine by optimizing the Nanotrap formulation, creating an ultimate therapeutic system for the virus.

"This is the starting point," Huang said. "We want to do something to help the world."

The research involved collaborators across departments, including chemistry, biology, and medicine.

Source:

University of Chicago

Journal reference:


Chen, M., et al. (2021) Nanotraps for the containment and clearance of SARS-CoV-2. Matter. doi.org/10.1016/j.matt.2021.04.005.
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Re: Is Nanotechnology helping in the fight against Covid 19, or Cancer?

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Targeting tumors with nanoworms

4/29/21


https://phys.org/news/2021-04-tumors-nanoworms.html


Drugs and vaccines circulate through the vascular system reacting according to their chemical and structural nature. In some cases, they are intended to diffuse. In other cases, like cancer treatments, the intended target is highly localized. The effectiveness of a medicine —and how much is needed and the side effects it causes —are a function of how well it can reach its target.

"A lot of medicines involve intravenous injections of drug carriers," said Ying Li, an assistant professor of mechanical engineering at the University of Connecticut. "We want them to be able to circulate and find the right place at the right time and to release the right amount of drugs to safely protect us. If you make mistakes, there can be terrible side effects."

Li studies nanomedicines and how they can be designed to work more efficiently. Nanomedicine involves the use of nanoscale materials, such as biocompatible nanoparticles and nanorobots, for diagnosis, delivery, sensing or actuation purposes in a living organism. His work harnesses the power of supercomputers to simulate the dynamics of nanodrugs in the blood stream, design new forms of nanoparticles, and find ways to control them.

Over the last decade, with support from the National Science Foundation, Li and his team have investigated many key aspects of nanomedicines, pioneering methods to model their flow and how they interact with structures within the body.

"My research is centered on how to build high-fidelity, high-performance computing platforms to understand the complicated behaviors of these materials and the biological systems down to the nanoscale," he said.

"I'm a 100% computational person, there's no dirty hands," Li said. "Because of the size of these particles, this problem is very hard to study using experiments."

Writing in Soft Matter in January 2021, Li described the results of a study that looked at how nanoparticles of various sizes and shapes —including nanoworms—move in blood vessels of different geometries, mimicking the constricted microvasculature. Nanoworms are long, thin, engineered encapsulations of drug contents.

"We found that the transport of these nanoworms is dominated by red blood cells," which make up 40% to 50% of the flow, Li explained. "It's like driving on the highway—construction slows down traffic. Drugs are getting carried by individual red blood cells and dragged into narrow regions and getting stuck."

He determined that nanoworms can travel more efficiently through the bloodstream, passing through blockages where spherical or flat shapes get stuck.

"The nanoworm moves like a snake. It can swim between red blood cells making it easier to escape tight spots," Li said.

Speed is of the essence—drugs must reach their destination before they are discovered and neutralized by the body's immune system, which is always on the hunt for foreign particles.

The first nanoparticle-based treatment to be FDA approved for cancer was Doxil—a formulation of the chemotherapy agent doxorubicin. Many more are currently in development. However, a 2016 study in Nature Reviews Materials found only 0.7% of an administered nanoparticle dose is delivered to a solid tumor.

"We know that anti-cancer drug molecules are highly toxic," Li said. "If they don't go to the right place, they hurt a lot. We can reduce the dosage if we actively guide the delivery."

Tailor-made shapes are one way to improve the delivery of cancer drugs. (Currently, 90% of administered nanoparticles are spherical.) Another way is to coax drugs to their target.

Li's team has computationally modeled nanoparticles that can be manipulated with a magnetic field. In a 2018 paper in the Proceedings of the Royal Society, they showed that even a small magnetic force could nudge the nanoparticles out of the blood flow, leading to a far greater number of particles reaching the right destination.

Li's work is powered by the Frontera supercomputer at the Texas Advanced Computing Center (TACC), the ninth fastest in the world. Li was an early user of the system when it launched in 2019, and has used Frontera continuously since then to perform a variety of simulations.

"We're building high-fidelity computational models on Frontera to understand the transport behavior of nanoparticles and nanoworms to see how they circulate in blood flow," Li said. His largest models are more than 1,000 micrometers long and include thousands of red blood cells, totaling billions of independent ways that the system can move.

"Advanced cyberinfrastructure resources, such as Frontera, enable researchers to experiment with novel frameworks and build innovative models that, in this example, help us understand the human circulatory system in a new way," said Manish Parashar, Director of the NSF Office for Advanced Cyberinfrastructure. "NSF supports Frontera as part of a broader ecosystem of cyberinfrastructure investments, including software and data analytics, that push the boundaries of science to yield insights with immediate application in our lives."

Frontera allows Li not only to run computational experiments, but also to develop a new computational framework that combines fluid dynamics and molecular dynamics.

Writing in Computer Physics Communications in 2020, he described OpenFSI: a highly efficient and portable fluid–structure simulation package based on the immersed-boundary method. The computational platform serves as a tool for the broader drug-design community and can be translated for many other engineering applications, such as additive manufacturing, chemical processing and underwater robotics.

"The current computational model covers many important processes, but the whole process is so complicated. If you consider a patient-specific vasculature network, that makes our computational model intractable," Li said.

He is taking advantage of artificial intelligence (AI) and machine learning to serve as a high-speed vehicle for the rapid generation of new nanoparticle designs and methods. Like all AI and machine learning, this approach requires massive quantities of data. In Li's case, the data is coming from simulations on Frontera.

"We're currently building the training database for the machine learning aspect of our work. We ran a lot of simulations with different scenarios to get broad training data," Li explained. "Then, we can pre-train the neural network using the hypothetical data we take from these simulations so they can quickly and efficiently predict the effects."

Li's typical simulations use 500 to 600 processors, though some aspects of the research requires up to 9,000 processors computing in parallel. "My research productivity is correlated with the speed of the system I use. Frontera has been fantastic."

When people picture medical research, they typically think of lab experiments or drug trials, but there are limitations to this type of work, whether economic or physical, Li said.

"The computational approach is getting more powerful and more predictive," he said. "We should take advantage of computational simulations before we run very expensive experiments to rationalize the problem and provide better guidance."

More information: Huilin Ye et al. Red blood cell hitchhiking enhances the accumulation of nano- and micro-particles in the constriction of a stenosed microvessel, Soft Matter (2020). DOI: 10.1039/d0sm01637c
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Re: Is Nanotechnology helping in the fight against Covid 19, or Cancer?

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Nanotechnology offers new hope for bowel cancer patients

5/3/21


https://phys.org/news/2021-05-nanotechn ... ients.html


Bowel cancer survival rates could be improved if chemotherapy drugs were delivered via tiny nanoparticles to the diseased organs rather than oral treatment.

That's the finding from Indian and Australian scientists who have undertaken the first study, using nanoparticles to target bowel cancer, the third most common cancer in the world and the second most deadliest.

The researchers have shown in animal experiments that nanoparticles containing the chemotherapy drug Capecitabine (CAP) attach themselves directly to the diseased cells, bypassing healthy cells and therefore reducing toxic side effects as well as the size and number of tumors.

The scientists, from the Manipal Academy of Higher Education, Indian Institute of Science and the University of South Australia, have published their findings in the journal Carbohydrate Polymers.

UniSA Professor of Pharmaceutical Science, Sanjay Garg—the sole Australian researcher involved in the project—says that CAP (otherwise known as Xeloda) is the first-line chemotherapy drug for bowel cancer. He co-supervised the Ph.D. scholar Reema Narayan, with Prof Usha Nayak from Manipal, India.

"Due to its short life, a high dose is necessary to maintain effective concentration, resulting in some harsh side effects when delivered conventionally, including severe hand and foot pain, dermatitis, nausea, vomiting, dizziness and loss of taste," Prof Garg says.

The side effects are exacerbated because the drug affects both healthy and diseased cells.

"A viable alternative to conventional therapy is targeted drug delivery using nanoparticles as smart carriers so that the drug can be delivered specifically to the tumor. This allows a smaller and less toxic dose," he says.

CAP delivered via nanoparticles reduces both the size and number of cancerous bowel tumors, results in fewer abnormal cells, improved red and white blood cell counts and less damage to other organs.

The targeted delivery system has a dual function: binding the receptors as well as releasing the drug to the tumor micro-environment.

"It has been a challenging project but we believe the platform technology developed can be applied to other cancers and chemotherapeutic drugs," Prof Garg says.

Approximately two million people are diagnosed with bowel cancer each year and half of those are not expected to survive, according to the World Health Organization. The risk factors include consuming processed meat, red meat and alcoholic drinks and obesity.

More information:
Reema Narayan et al. Chitosan-glucuronic acid conjugate coated mesoporous silica nanoparticles: A smart pH-responsive and receptor-targeted system for colorectal cancer therapy, Carbohydrate Polymers (2021). DOI: 10.1016/j.carbpol.2021.117893
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Re: Is Nanotechnology helping in the fight against Covid 19, or Cancer?

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Researchers develop new graphite-based sensor technology for wearable medical devices

5/4/21


https://phys.org/news/2021-05-graphite- ... dical.html


Researchers at AMBER, the SFI Centre for Advanced Materials and BioEngineering Research, and from Trinity's School of Physics, have developed next-generation, graphene-based sensing technology using their innovative G-Putty material.

The team's printed sensors are 50 times more sensitive than the industry standard and outperform other comparable nano-enabled sensors in an important metric seen as a game-changer in the industry: flexibility.

Maximising sensitivity and flexibility without reducing performance makes the teams' technology an ideal candidate for the emerging areas of wearable electronics and medical diagnostic devices.

The team—led by Professor Jonathan Coleman from Trinity's School of Physics, one of the world's leading nanoscientists—demonstrated that they can produce a low-cost, printed, graphene nanocomposite strain sensor.

Creating and testing inks of different viscosities (runniness) the team found that they could tailor G-Putty inks according to printing technology and application.

They published their results in the journal Small.

In medical settings, strain sensors are a highly valuable diagnostic tool used to measure changes in mechanical strain such as pulse rate, or the changes in a stroke victim's ability to swallow. A strain sensor works by detecting this mechanical change and converting it into a proportional electrical signal, thereby acting as mechanical-electrical converter.

While strain sensors are currently available on the market they are mostly made from metal foil that poses limitations in terms wearability, versatility, and sensitivity.

Professor Coleman said:

"My team and I have previously created nanocomposites of graphene with polymers like those found in rubberbands and silly putty. We have now turned G-putty, our highly malleable graphene blended silly putty, into an ink blend that has excellent mechanical and electrical properties. Our inks have the advantage that they can be turned into a working device using industrial printing methods, from screen printing, to aerosol and mechanical deposition.

"An additional benefit of our very low cost system is that we can control a variety of different parameters during the manufacturing process, which gives us the ability to tune the sensitivity of our material for specific applications calling for detection of really minute strains."

Current market trends in the global medical device market indicate that this research is well placed within the move to personalised, tuneable, wearable sensors that can easily be incorporated into clothing or worn on skin.

In 2020 the wearable medical device market was valued at USD $16 billion with expectations for significant growth particularly in remote patient monitoring devices and an increasing focus on fitness and lifestyle monitoring.

The team is ambitious in translating the scientific work into product. Dr. Daniel O'Driscoll, Trinity's School of Physics, added:

"The development of these sensors represents a considerable step forward for the area of wearable diagnostic devices—devices which can be printed in custom patterns and comfortably mounted to a patient's skin to monitor a range of different biological processes.

"We're currently exploring applications to monitor real-time breathing and pulse, joint motion and gait, and early labour in pregnancy. Because our sensors combine high sensitivity, stability and a large sensing range with the ability to print bespoke patterns onto flexible, wearable substrates, we can tailor the sensor to the application. The methods used to produce these devices are low cost and easily scalable—essential criteria for producing a diagnostic device for wide scale use."

More information: Daniel P. O'Driscoll et al. Printable G‐Putty for Frequency‐ and Rate‐Independent, High‐Performance Strain Sensors, Small (2021). DOI: 10.1002/smll.202006542
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