Tag Archives: Polytechnique Montréal

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.

The State of Science and Technology (S&T) and Industrial Research and Development (IR&D) in Canada

Earlier this year I featured (in a July 1, 2016 posting) the announcement of a third assessment of science and technology in Canada by the Council of Canadian Academies. At the time I speculated as to the size of the ‘expert panel’ making the assessment as they had rolled a second assessment (Industrial Research and Development) into this one on the state of science and technology. I now have my answer thanks to an Oct. 17, 2016 Council of Canadian Academies news release announcing the chairperson (received via email; Note: Links have been removed and emphases added for greater readability),

The Council of Canadian Academies (CCA) is pleased to announce Dr. Max Blouw, President and Vice-Chancellor of Wilfrid Laurier University, as Chair of the newly appointed Expert Panel on the State of Science and Technology (S&T) and Industrial Research and Development (IR&D) in Canada.

“Dr. Blouw is a widely respected leader with a strong background in research and academia,” said Eric M. Meslin, PhD, FCAHS, President and CEO of the CCA. “I am delighted he has agreed to serve as Chair for an assessment that will contribute to the current policy discussion in Canada.”

As Chair of the Expert Panel, Dr. Blouw will work with the multidisciplinary, multi-sectoral Expert Panel to address the following assessment question, referred to the CCA by Innovation, Science and Economic Development Canada (ISED):

What is the current state of science and technology and industrial research and development in Canada?

Dr. Blouw will lead the CCA Expert Panel to assess the available evidence and deliver its final report by late 2017. Members of the panel include experts from different fields of academic research, R&D, innovation, and research administration. The depth of the Panel’s experience and expertise, paired with the CCA’s rigorous assessment methodology, will ensure the most authoritative, credible, and independent response to the question.

“I am very pleased to accept the position of Chair for this assessment and I consider myself privileged to be working with such an eminent group of experts,” said Dr. Blouw. “The CCA’s previous reports on S&T and IR&D provided crucial insights into Canada’s strengths and weaknesses in these areas. I look forward to contributing to this important set of reports with new evidence and trends.”

Dr. Blouw was Vice-President Research, Associate Vice-President Research, and Professor of Biology, at the University of Northern British Columbia, before joining Wilfrid Laurier as President. Dr. Blouw served two terms as the chair of the university advisory group to Industry Canada and was a member of the adjudication panel for the Ontario Premier’s Discovery Awards, which recognize the province’s finest senior researchers. He recently chaired the International Review Committee of the NSERC Discovery Grants Program.

For a complete list of Expert Panel members, their biographies, and details on the assessment, please visit the assessment page. The CCA’s Member Academies – the Royal Society of Canada, the Canadian Academy of Engineering, and the Canadian Academy of Health Sciences – are a key source of membership for expert panels. Many experts are also Fellows of the Academies.

The Expert Panel on the State of S&T and IR&D
Max Blouw, (Chair) President and Vice-Chancellor of Wilfrid Laurier University
Luis Barreto, President, Dr. Luis Barreto & Associates and Special Advisor, NEOMED-LABS
Catherine Beaudry, Professor, Department of Mathematical and Industrial Engineering, Polytechnique Montréal
Donald Brooks, FCAHS, Professor, Pathology and Laboratory Medicine, and Chemistry, University of British Columbia
Madeleine Jean, General Manager, Prompt
Philip Jessop, FRSC, Professor, Inorganic Chemistry and Canada Research Chair in Green Chemistry, Department of Chemistry, Queen’s University; Technical Director, GreenCentre Canada
Claude Lajeunesse, FCAE, Corporate Director and Interim Chair of the Board of Directors, Atomic Energy of Canada Ltd.
Steve Liang, Associate Professor, Geomatics Engineering, University of Calgary; Director, GeoSensorWeb Laboratory; CEO, SensorUp Inc.
Robert Luke, Vice-President, Research and Innovation, OCAD University
Douglas Peers, Professor, Dean of Arts, Department of History, University of Waterloo
John M. Thompson, O.C., FCAE, Retired Executive Vice-Chairman, IBM Corporation
Anne Whitelaw, Associate Dean Research, Faculty of Fine Arts and Associate Professor, Department of Art History, Concordia University
David A. Wolfe, Professor, Political Science and Co-Director, Innovation Policy Lab, Munk School of Global Affairs, University of Toronto

You can find more information about the expert panel here and about this assessment and its predecesors here.

A few observations, given the size of the task this panel is lean. As well, there are three women in a group of 13 (less than 25% representation) in 2016? It’s Ontario and Québec-dominant; only BC and Alberta rate a representative on the panel. I hope they will find ways to better balance this panel and communicate that ‘balanced story’ to the rest of us. On the plus side, the panel has representatives from the humanities, arts, and industry in addition to the expected representatives from the sciences.

Very precise nanorobots redefine the administration of anti-cancer drugs

A very exuberant announcement has been made about cancer drug delivery by precise nanorobots, which have been tested in mice, in an Aug. 15, 2016 news item on ScienceDaily,

Researchers from Polytechnique Montréal, Université de Montréal and McGill University have just achieved a spectacular breakthrough in cancer research. They have developed new nanorobotic agents capable of navigating through the bloodstream to administer a drug with precision by specifically targeting the active cancerous cells of tumours. This way of injecting medication ensures the optimal targeting of a tumour and avoids jeopardizing the integrity of organs and surrounding healthy tissues. As a result, the drug dosage that is highly toxic for the human organism could be significantly reduced.

This scientific breakthrough has just been published in the prestigious journal Nature Nanotechnology in an article titled “Magneto-aerotactic bacteria deliver drug-containing nanoliposomes to tumour hypoxic regions.” The article notes the results of the research done on mice, which were successfully administered nanorobotic agents into colorectal tumours.

An Aug. 15, 2016 Polytechnique Montréal news release (also on EurekAlert), which originated the news item, describes the work and the nanorobots or nanorobotic agents (bacteria) in more detail,

“These legions of nanorobotic agents were actually composed of more than 100 million flagellated bacteria – and therefore self-propelled – and loaded with drugs that moved by taking the most direct path between the drug’s injection point and the area of the body to cure,” explains Professor Sylvain Martel, holder of the Canada Research Chair in Medical Nanorobotics and Director of the Polytechnique Montréal Nanorobotics Laboratory, who heads the research team’s work. “The drug’s propelling force was enough to travel efficiently and enter deep inside the tumours.”

When they enter a tumour, the nanorobotic agents can detect in a wholly autonomous fashion the oxygen-depleted tumour areas, known as hypoxic zones, and deliver the drug to them. This hypoxic zone is created by the substantial consumption of oxygen by rapidly proliferative tumour cells. Hypoxic zones are known to be resistant to most therapies, including radiotherapy.

But gaining access to tumours by taking paths as minute as a red blood cell and crossing complex physiological micro-environments does not come without challenges. So Professor Martel and his team used nanotechnology to do it.

Bacteria with compass

To move around, bacteria used by Professor Martel’s team rely on two natural systems. A kind of compass created by the synthesis of a chain of magnetic nanoparticles allows them to move in the direction of a magnetic field, while a sensor measuring oxygen concentration enables them to reach and remain in the tumour’s active regions. By harnessing these two transportation systems and by exposing the bacteria to a computer-controlled magnetic field, researchers showed that these bacteria could perfectly replicate artificial nanorobots of the future designed for this kind of task.

“This innovative use of nanotransporters will have an impact not only on creating more advanced engineering concepts and original intervention methods, but it also throws the door wide open to the synthesis of new vehicles for therapeutic, imaging and diagnostic agents,” Professor Martel adds. “Chemotherapy, which is so toxic for the entire human body, could make use of these natural nanorobots to move drugs directly to the targeted area, eliminating the harmful side effects while also boosting its therapeutic effectiveness.”

This news contrasts somewhat with research at the University of Toronto (my April 27, 2016 posting) investigating how many drug-carrying nanoparticles find the cancer tumours they are intended for. The answer was that less than 1% make their way to the tumour and the conclusion those scientists reached was that we don’t know enough about how materials are delivered to the cells. My question, are the bacteria/nanorobots better at finding the tumours/cells? It’s not clear from the news release.

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

Magneto-aerotactic bacteria deliver drug-containing nanoliposomes to tumour hypoxic regions by Ouajdi Felfoul, Mahmood Mohammadi, Samira Taherkhani, Dominic de Lanauze, Yong Zhong Xu, Dumitru Loghin, Sherief Essa, Sylwia Jancik, Daniel Houle, Michel Lafleur, Louis Gaboury, Maryam Tabrizian, Neila Kaou, Michael Atkin, Té Vuong, Gerald Batist, Nicole Beauchemin, Danuta Radzioch, & Sylvain Martel. Nature Nanotechnology (2016)  doi:10.1038/nnano.2016.137 Published online 15 August 2016

This paper is behind a paywall.

Nanotechnology and cybersecurity risks

Gregory Carpenter has written a gripping (albeit somewhat exaggerated) piece for Signal, a publication of the  Armed Forces Communications and Electronics Association (AFCEA) about cybersecurity issues and  nanomedicine endeavours. From Carpenter’s Jan. 1, 2016 article titled, When Lifesaving Technology Can Kill; The Cyber Edge,

The exciting advent of nanotechnology that has inspired disruptive and lifesaving medical advances is plagued by cybersecurity issues that could result in the deaths of people that these very same breakthroughs seek to heal. Unfortunately, nanorobotic technology has suffered from the same security oversights that afflict most other research and development programs.

Nanorobots, or small machines [or nanobots[, are vulnerable to exploitation just like other devices.

At the moment, the issue of cybersecurity exploitation is secondary to making nanobots, or nanorobots, dependably functional. As far as I’m aware, there is no such nanobot. Even nanoparticles meant to function as packages for drug delivery have not been perfected (see one of the controversies with nanomedicine drug delivery described in my Nov. 26, 2015 posting).

That said, Carpenter’s point about cybersecurity is well taken since security features are often overlooked in new technology. For example, automated banking machines (ABMs) had woefully poor (inadequate, almost nonexistent) security when they were first introduced.

Carpenter outlines some of the problems that could occur, assuming some of the latest research could be reliably  brought to market,

The U.S. military has joined the fray of nanorobotic experimentation, embarking on revolutionary research that could lead to a range of discoveries, from unraveling the secrets of how brains function to figuring out how to permanently purge bad memories. Academia is making amazing advances as well. Harnessing progress by Harvard scientists to move nanorobots within humans, researchers at the University of Montreal, Polytechnique Montreal and Centre Hospitalier Universitaire Sainte-Justine are using mobile nanoparticles inside the human brain to open the blood-brain barrier, which protects the brain from toxins found in the circulatory system.

A different type of technology presents a risk similar to the nanoparticles scenario. A DARPA-funded program known as Restoring Active Memory (RAM) addresses post-traumatic stress disorder, attempting to overcome memory deficits by developing neuroprosthetics that bridge gaps in an injured brain. In short, scientists can wipe out a traumatic memory, and they hope to insert a new one—one the person has never actually experienced. Someone could relish the memory of a stroll along the French Riviera rather than a terrible firefight, even if he or she has never visited Europe.

As an individual receives a disruptive memory, a cyber criminal could manage to hack the controls. Breaches of the brain could become a reality, putting humans at risk of becoming zombie hosts [emphasis mine] for future virus deployments. …

At this point, the ‘zombie’ scenario Carpenter suggests seems a bit over-the-top but it does hearken to the roots of the zombie myth where the undead aren’t mindlessly searching for brains but are humans whose wills have been overcome. Mike Mariani in an Oct. 28, 2015 article for The Atlantic has presented a thought-provoking history of zombies,

… the zombie myth is far older and more rooted in history than the blinkered arc of American pop culture suggests. It first appeared in Haiti in the 17th and 18th centuries, when the country was known as Saint-Domingue and ruled by France, which hauled in African slaves to work on sugar plantations. Slavery in Saint-Domingue under the French was extremely brutal: Half of the slaves brought in from Africa were worked to death within a few years, which only led to the capture and import of more. In the hundreds of years since, the zombie myth has been widely appropriated by American pop culture in a way that whitewashes its origins—and turns the undead into a platform for escapist fantasy.

The original brains-eating fiend was a slave not to the flesh of others but to his own. The zombie archetype, as it appeared in Haiti and mirrored the inhumanity that existed there from 1625 to around 1800, was a projection of the African slaves’ relentless misery and subjugation. Haitian slaves believed that dying would release them back to lan guinée, literally Guinea, or Africa in general, a kind of afterlife where they could be free. Though suicide was common among slaves, those who took their own lives wouldn’t be allowed to return to lan guinée. Instead, they’d be condemned to skulk the Hispaniola plantations for eternity, an undead slave at once denied their own bodies and yet trapped inside them—a soulless zombie.

I recommend reading Mariani’s article although I do have one nit to pick. I can’t find a reference to brain-eating zombies until George Romero’s introduction of the concept in his movies. This Zombie Wikipedia entry seems to be in agreement with my understanding (if I’m wrong, please do let me know and, if possible, provide a link to the corrective text).

Getting back to Carpenter and cybersecurity with regard to nanomedicine, while his scenarios may seem a trifle extreme it’s precisely the kind of thinking you need when attempting to anticipate problems. I do wish he’d made clear that the technology still has a ways to go.

A race to find substitutes for graphene?

I have two items concerning research which seeks to replace graphene in one application or other.

Black phosporus and the École Polytechniqe de Montréal

A June 2, 2015 news item on Nanotechnology Now features work on developing a two-dimensional black phosphorus material, 2D phosphane,

A team of researchers from Universite de Montreal, Polytechnique Montreal and the Centre national de la recherche scientifique (CNRS) in France is the first to succeed in preventing two-dimensional layers of black phosphorus from oxidating. In so doing, they have opened the doors to exploiting their striking properties in a number of electronic and optoelectronic devices. …

Black phosphorus, a stable allotrope of phosphorus that presents a lamellar structure similar to that of graphite, has recently begun to capture the attention of physicists and materials researchers. It is possible to obtain single atomic layers from it, which researchers call 2D phosphane. A cousin of the widely publicized graphene, 2D phosphane brings together two very sought-after properties for device design.

A June 2, 2015 École Polytechniqe de Montréal news release, which originated the news item, expands on why 2D phosphane is an appealing material,

First, 2D phosphane is a semiconductor material that provides the necessary characteristics for making transistors and processors. With its high-mobility, it is estimated that 2D phosphane could form the basis for electronics that is both high-performance and low-cost.

Furthermore, this new material features a second, even more distinctive, characteristic: its interaction with light depends on the number of atomic layers used. One monolayer will emit red light, whereas a thicker sample will emit into the infrared. This variation makes it possible to manufacture a wide range of optoelectronic devices, such as lasers or detectors, in a strategic fraction of the electromagnetic spectrum.

The news release goes on to describe an important issue with phosphane and how the scientists addressed it,

Until now, the study of 2D phosphane’s properties was slowed by a major problem: in ambient  conditions, very thin layers of the material would degrade, to the point of compromising its future in the industry despite its promising potential.

As such, the research team has made a major step forward by succeeding in determining the physical mechanisms at play in this degradation, and in identifying the key elements that lead to the layers’ oxidation.

“We have demonstrated that 2D phosphane undergoes oxidation under ambient conditions, caused jointly by the presence of oxygen, water and light. We have also characterized the phenomenon’s evolution over time by using electron beam spectroscopy and Raman spectroscopy,” reports Professor Richard Martel of Université de Montréal’s Department of Chemistry.

Next, the researchers developed an efficient procedure for producing these very fragile single-atom layers and keeping them intact.

“We were able to study the vibration modes of the atoms in this new material. Since earlier studies had been carried out on heavily degraded materials, we revealed the as-yet-unsuspected effects of quantum confinement on atoms’ vibration modes,” notes Professor Sébastien Francoeur of Polytechnique’s Department of Engineering Physics.

The study’s results will help the world scientific community develop 2D phosphane’s very special properties with the aim of developing new nanotechnologies that could give rise to high-performance microprocessors, lasers, solar cells and more.

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

Photooxidation and quantum confinement effects in exfoliated black phosphorus by Alexandre Favron, Etienne Gaufrès, Frédéric Fossard, Anne-Laurence Phaneuf-L’Heureux, Nathalie Y-W. Tang, Pierre L. Lévesque, Annick Loiseau, Richard Leonelli, Sébastien Francoeur, & Richard Martel. Nature Materials (2015)  doi:10.1038/nmat4299 Published online 25 May 2015

This paper is behind a paywall.

Now. for the second item about replacing graphene.

China’s new aerogel, a rival to graphene aerogels?

A June 2, 2015 American Institute of Physics news release (also on EurekAlert) describes research into an alternative to expensive graphene aerogels,

The electromagnetic radiation discharged by electronic equipment and devices is known to hinder their smooth operation. Conventional materials used today to shield from incoming electromagnetic waves tend to be sheets of metal or composites, which rely on reflection as a shielding mechanism.

But now, materials such as graphene aerogels are gaining traction as more desirable alternatives because they act as electromagnetic absorbers. They’re widely expected to improve energy storage, sensors, nanoelectronics, catalysis and separations, but graphene aerogels are prohibitively expensive and difficult to produce for large-scale applications because of the complicated purification and functionalization steps involved in their fabrication.

So a team of researchers in China set out to design a cheaper material with properties similar to a graphene aerogel–in terms of its conductivity, as well as a lightweight, anticorrosive, porous structure. In the journal Applied Physics Letters, from AIP Publishing, the researchers describe the new material they created and its performance.

Aming Xie, an expert in organic chemistry, and Fan Wu, both affiliated with PLA University of Science and Technology, worked with colleagues at Nanjing University of Science and Technology to tap into organic chemistry and conducting polymers to fabricate a three-dimensional (3-D) polypyrrole (PPy) aerogel-based electromagnetic absorber.

They chose to concentrate on this method because it enables them to “regulate the density and dielectric property of conducting polymers through the formation of pores during the oxidation polymerization of the pyrrole monomer,” explained Wu.

And the fabrication process is a simple one. “It requires only four common chemical reagents: pyrrole, ferric chloride (FeCl3), ethanol and water — which makes it cheap enough and enables large-scale fabrication,” Wu said. “We’re also able to pour the FeCl3 solution directly into the pyrrole solution — not drop by drop — to force the pyrrole to polymerize into a 3-D aerogel rather than PPy particles.”

In short, the team’s 3-D PPy aerogel is designed to exhibit “desirable properties such as a porous structure and low density,” Wu noted.

Beyond that, its electromagnetic absorption performance — with low loss — shows great promise. “We believe a ‘wide’ absorption range is more useful than high absorption within one frequency,” Wu said. Compared with previous works, the team’s new aerogel has the lowest adjunction and widest effective bandwidth — with a reflection loss below -10 decibels.

In terms of applications, based on the combination of low adjunction and a “wide” effective bandwidth, the researchers expect to see their 3-D PPy aerogel used in surface coatings for aircraft.

Another potential application is as coatings within the realm of corrosion prevention and control. “Common anticorrosion coatings contain a large amount of zinc (70 to 80 percent by weight), and these particles not only serve as a cathode by corroding to protect the iron structure but also to maintain a suitable conductivity for the electrochemistry process,” Wu pointed out. “If our 3-D PPy aerogel could build a conductivity network in this type of coating, the loss of zinc particles could be rapidly reduced.”

The team is now taking their work a step further by pursuing a 3-D PPy/PEDOT-based (poly(3,4-ethylenedioxythiophene) electromagnetic absorber. “Our goal is to grow solid-state polymerized PEDOT particles in the holes of the 3-D PPy aerogel formed by PPy chains,” Wu added.

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

Self-assembled ultralight three-dimensional polypyrrole aerogel for effective electromagnetic absorption by Aming Xie, Fan Wu, Mengxiao Sun, Xiaoqing Dai, Zhuanghu Xu, Yanyu Qiu, Yuan Wang, and Mingyang Wang. Appl. Phys. Lett. 106, 222902 (2015); http://dx.doi.org/10.1063/1.4921180

This paper is open access.

Université de Montréal (Canada) and nanobots breech blood-brain barrier to deliver drugs to the brain

In the spirit of full disclosure, the March 25, 2014 news item on ScienceDaily describing the research about breeching the blood-brain barrier uses the term nanorobotic agents rather than nanobots, a term which makes my headline a lot catchier although less accurate. Getting back to the research,

Magnetic nanoparticles can open the blood-brain barrier and deliver molecules directly to the brain, say researchers from the University of Montreal, Polytechnique Montréal, and CHU Sainte-Justine. This barrier runs inside almost all vessels in the brain and protects it from elements circulating in the blood that may be toxic to the brain. The research is important as currently 98% of therapeutic molecules are also unable to cross the blood-brain barrier.

“The barrier is temporary [sic] opened at a desired location for approximately 2 hours by a small elevation of the temperature generated by the nanoparticles when exposed to a radio-frequency field,” explained first author and co-inventor Seyed Nasrollah Tabatabaei. “Our tests revealed that this technique is not associated with any inflammation of the brain. This new result could lead to a breakthrough in the way nanoparticles are used in the treatment and diagnosis of brain diseases,” explained the co-investigator, Hélène Girouard. “At the present time, surgery is the only way to treat patients with brain disorders. Moreover, while surgeons are able to operate to remove certain kinds of tumors, some disorders are located in the brain stem, amongst nerves, making surgery impossible,” added collaborator and senior author Anne-Sophie Carret.

A March 25, 2015 University of Montreal news release (also on EurekAlert), which originated the news item, notes that the technique was tested or rats or mice (murine model) and explains how the technology breeches the blood-brain barrier,

Although the technology was developed using murine models and has not yet been tested in humans, the researchers are confident that future research will enable its use in people. “Building on earlier findings and drawing on the global effort of an interdisciplinary team of researchers, this technology proposes a modern version of the vision described almost 40 years ago in the movie Fantastic Voyage, where a miniature submarine navigated in the vascular network to reach a specific region of the brain,” said principal investigator Sylvain Martel. In earlier research, Martel and his team had managed to manipulate the movement of nanoparticles through the body using the magnetic forces generated by magnetic resonance imaging (MRI) machines.

To open the blood-brain barrier, the magnetic nanoparticles are sent to the surface of the blood-brain barrier at a desired location in the brain. Although it was not the technique used in this study, the placement could be achieved by using the MRI technology described above. Then, the researchers generated a radio-frequency field. The nanoparticles reacted to the radio-frequency field by dissipating heat thereby creating a mechanical stress on the barrier. This allows a temporary and localized opening of the barrier for diffusion of therapeutics into the brain.

The technique is unique in many ways. “The result is quite significant since we showed in previous experiments that the same nanoparticles can also be used to navigate therapeutic agents in the vascular network using a clinical MRI scanner,” Martel remarked. “Linking the navigation capability with these new results would allow therapeutics to be delivered directly to a specific site of the brain, potentially improving significantly the efficacy of the treatment while avoiding systemic circulation of toxic agents that affect healthy tissues and organs,” Carret added. “While other techniques have been developed for delivering drugs to the blood-brain barrier, they either open it too wide, exposing the brain to great risks, or they are not precise enough, leading to scattering of the drugs and possible unwanted side effect,” Martel said.

Although there are many hurdles to overcome before the technology can be used to treat humans, the research team is optimistic. “Although our current results are only proof of concept, we are on the way to achieving our goal of developing a local drug delivery mechanism that will be able to treat oncologic, psychiatric, neurological and neurodegenerative disorders, amongst others,” Carret concluded.

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

Remote control of the permeability of the blood–brain barrier by magnetic heating of nanoparticles: A proof of concept for brain drug delivery by Seyed Nasrollah Tabatabaei, Hélène Girouard, Anne-Sophie Carret, and Sylvain Martel.Journal of Controlled Release, Volume 206, 28 May 2015, Pages 49–57,  DOI: 10.1016/j.jconrel.2015.02.027  Available online 25 February 2015

This paper is behind a paywall.

For anyone unfamiliar with French, University of Montreal is Université de Montréal.

Nanosurgery in Montréal (Canada)

When I was typing up charts for home nursing care (nurses visiting patients in their home after a hospital procedure), I routinely asked if a patient whose cancer had metastasized would require palliative care even though the answer would be yes. In over 3 years and after hundreds of charts, I only had one ‘No’. So it is with some interest I read about Michel Meunier and his team’s work at the Polytechnique Montréal (Québec, Canada). From the Feb. 16, 2012 news item on Nanowerk,

The unique method developed by Professor Michel Meunier and his team uses a femtosecond laser (a laser with ultra-short pulses) along with gold nanoparticles. Deposited on the cells, these nanoparticles concentrate the laser’s energy and make it possible to perform nanometric-scale surgery in an extremely precise and non-invasive fashion. The technique allows to change the expression of genes in the cancer cells and could be used to slow their migration and prevent the formation of metastases.

The technique perfected by Professor Meunier and his colleagues is a promising alternative to conventional cellular transfection methods, such as lipofection. The experiment, carried out in Montréal laboratories on malignant human melanoma cells, demonstrated 70% optoporation effectiveness, as well as a transfection performance three times higher than lipofection treatment. In addition, unlike conventional treatment, which destroys the physical integrity of the cells, the new method assures cellular viability, with a toxicity of less than 1%.

The Polytechnique’s Feb. 16, 2012 press release is here and you can find out more about Meunier and his lab here (in English and en français). For those eager to read the article, it was published in Biomaterials (vol. 33, no. 7, March 2012, pp. 2345-50) is titled, Off-resonance plasmonic enhanced femtosecond laser optoporation and transfection of cancer cells and is behind a paywall.