Tag Archives: Au nanoparticles

Put a ring on it: preventing clumps of gold nanoparticles

Caption: A comparison of how linear PEG (left) and cyclic PEG (right) attach to a gold nanoparticle Credit: Yubo Wang, Takuya Yamamoto

A January 20, 2021 news item on phys.org focuses on work designed to stop gold nanoparticles from clumping together (Note: A link has been removed),

Hokkaido University scientists have found a way to prevent gold nanoparticles from clumping, which could help towards their use as an anti-cancer therapy.

Attaching ring-shaped synthetic compounds to gold nanoparticles helps them retain their essential light-absorbing properties, Hokkaido University researchers report in the journal Nature Communications.

A January 20, 2021 Hokkaido University press release (also on EurekAlert but published Jan. 21, 2020), which originated the news item, elaborates on the work,

Metal nanoparticles have unique light-absorbing properties, making them interesting for a wide range of optical, electronic and biomedical applications. For example, if delivered to a tumour, they could react with applied light to kill cancerous tissue. A problem with this approach, though, is that they easily clump together in solution, losing their ability to absorb light. This clumping happens in response to a variety of factors, including temperature, salt concentration and acidity.

Scientists have been trying to find ways to ensure nanoparticles stay dispersed in their target environments. Covering them with polyethylene glycol, otherwise known as PEG, has been relatively successful at this in the case of gold nanoparticles. PEG is biocompatible and can prevent gold surfaces from clumping together in the laboratory and in living organisms, but improvements are still needed.

Applied chemist Takuya Yamamoto and colleagues at Hokkaido University, The University of Tokyo, and Tokyo Institute of Technology found that mixing gold nanoparticles with ring-shaped PEG, rather than the normally linear PEG, significantly improved dispersion. The ‘cyclic-PEG’ (c-PEG) attaches to the surfaces of the nanoparticles without forming chemical bonds with them, a process called physisorption. The coated nanoparticles remained dispersed when frozen, freeze-dried and heated.

The team tested the c-PEG-covered gold nanoparticles in mice and found that they cleared slowly from the blood and accumulated better in tumours compared to gold nanoparticles coated with linear PEG. However, accumulation was lower than desired levels, so the researchers recommend further investigations to fine-tune the nanoparticles for this purpose.

Associate Professor Takuya Yamamoto is part of the Laboratory of Chemistry of Molecular Assemblies at Hokkaido University, where he studies the properties and applications of various cyclic chemical compounds.

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

Enhanced dispersion stability of gold nanoparticles by the physisorption of cyclic poly(ethylene glycol) by Yubo Wang, Jose Enrico Q. Quinsaat, Tomoko Ono, Masatoshi Maeki, Manabu Tokeshi, Takuya Isono, Kenji Tajima, Toshifumi Satoh, Shin-ichiro Sato, Yutaka Miura & Takuya Yamamoto. Nature Communications volume 11, Article number: 6089 (2020) DOI: https://doi.org/10.1038/s41467-020-19947-8 Published: 30 November 2020

This paper is open access.

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.

Non-viral ocular gene therapy with gold nanoparticles and femtosecond lasers

I love the stylistic choice the writer made (pay special attention to the second paragraph) when producing this November 19, 2018 Polytechnique Montréal news release (also on EurekAlert),

A scientific breakthrough by Professor Michel Meunier of Polytechnique Montréal and his collaborators offers hope for people with glaucoma, retinitis or macular degeneration.

In January 2009, the life of engineer Michel Meunier, a professor at Polytechnique Montréal, changed dramatically. Like others, he had observed that the extremely short pulse of a femtosecond laser (0.000000000000001 second) could make nanometre-sized holes appear in silicon when it was covered by gold nanoparticles. But this researcher, recognized internationally for his skills in laser and nanotechnology, decided to go a step further with what was then just a laboratory curiosity. He wondered if it was possible to go from silicon to living matter, from inorganic to organic. Could the gold nanoparticles and the femtosecond laser, this “light scalpel,” reproduce the same phenomenon with living cells?

A very pretty image illustrating the work,

Caption: Gold nanoparticles, which act like “nanolenses,” concentrate the energy produced by the extremely short pulse of a femtosecond laser to create a nanoscale incision on the surface of the eye’s retina cells. This technology, which preserves cell integrity, can be used to effectively inject drugs or genes into specific areas of the eye, offering new hope to people with glaucoma, retinitis or macular degeneration. Credit and Copyright: Polytechnique Montréal

The news release goes on to describe the technology in more detail,

Professor Meunier started working on cells in vitro in his Polytechnique laboratory. The challenge was to make a nanometric incision in the cells’ extracellular membrane without damaging it. Using gold nanoparticles that acted as “nanolenses,” Professor Meunier realized that it was possible to concentrate the light energy coming from the laser at a wavelength of 800 nanometres. Since there is very little energy absorption by the cells at this wavelength, their integrity is preserved. Mission accomplished!

Based on this finding, Professor Meunier decided to work on cells in vivo, cells that are part of a complex living cell structure, such as the eye for example.

The eye and the light scalpel

In April 2012, Professor Meunier met Przemyslaw Sapieha, an internationally renowned eye specialist, particularly recognized for his work on the retina. “Mike”, as he goes by, is a professor in the Department of Ophthalmology at Université de Montréal and a researcher at Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l’Est-de-l’Île-de-Montréal. He immediately saw the potential of this new technology and everything that could be done in the eye if you could block the ripple effect that occurs following a trigger that leads to glaucoma or macular degeneration, for example, by injecting drugs, proteins or even genes.

Using a femtosecond laser to treat the eye–a highly specialized and fragile organ–is very complex, however. The eye is part of the central nervous system, and therefore many of the cells or families of cells that compose it are neurons. And when a neuron dies, it does not regenerate like other cells do. Mike Sapieha’s first task was therefore to ensure that a femtosecond laser could be used on one or several neurons without affecting them. This is what is referred to as “proof of concept.”

Proof of concept

Mike and Michel called on biochemistry researcher Ariel Wilson, an expert in eye structures and vision mechanisms, as well as Professor Santiago Costantino and his team from the Department of Ophthalmology at Université de Montréal and the CIUSSS de l’Est-de-l’Île-de-Montréal for their expertise in biophotonics. The team first decided to work on healthy cells, because they are better understood than sick cells. They injected gold nanoparticles combined with antibodies to target specific neuronal cells in the eye, and then waited for the nanoparticles to settle around the various neurons or families of neurons, such as the retina. Following the bright flash generated by the femtosecond laser, the expected phenomenon occurred: small holes appeared in the cells of the eye’s retina, making it possible to effectively inject drugs or genes in specific areas of the eye. It was another victory for Michel Meunier and his collaborators, with these conclusive results now opening the path to new treatments.

The key feature of the technology developed by the researchers from Polytechnique and CIUSSS de l’Est-de-l’Île-de-Montréal is its extreme precision. With the use of functionalized gold nanoparticles, the light scalpel makes it possible to precisely locate the family of cells where the doctor will have to intervene.

Having successfully demonstrated proof of concept, Professor Meunier and his team filed a patent application in the United States. This tremendous work was also the subject of a paper reviewed by an impressive reading committee and published in the renowned journal Nano Letters in October 2018.

While there is still a lot of research to be done–at least 10 years’ worth, first on animals and then on humans–this technology could make all the difference in an aging population suffering from eye deterioration for which there are still no effective long-term treatments. It also has the advantage of avoiding the use of viruses commonly employed in gene therapy. These researchers are looking at applications of this technology in all eye diseases, but more particularly in glaucoma, retinitis and macular degeneration.

This light scalpel is unprecedented.

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

In Vivo Laser-Mediated Retinal Ganglion Cell Optoporation Using KV1.1 Conjugated Gold Nanoparticles by Ariel M. Wilson, Javier Mazzaferri, Éric Bergeron, Sergiy Patskovsky, Paule Marcoux-Valiquette, Santiago Costantino, Przemyslaw Sapieha, Michel Meunier. Nano Lett.201818116981-6988 DOI: https://doi.org/10.1021/acs.nanolett.8b02896 Publication Date: October 4, 2018  Copyright © 2018 American Chemical Society

This paper is behind a paywall.