Tag Archives: cancer

Microbubbles reform into nanoparticles after bursting

It seems researchers at the Toronto-based (Canada), Princess Margaret Cancer Centre, have developed a new theranostic tool made of microbubbles used for imaging that are then burst into nanoparticles delivering therapeutics. From a March 30, 2015 news item on phys.org,

Biomedical researchers led by Dr. Gang Zheng at Princess Margaret Cancer Centre have successfully converted microbubble technology already used in diagnostic imaging into nanoparticles that stay trapped in tumours to potentially deliver targeted, therapeutic payloads.

The discovery, published online today [March 30, 2015] in Nature Nanotechnology, details how Dr. Zheng and his research team created a new type of microbubble using a compound called porphyrin – a naturally occurring pigment in nature that harvests light.

A March 30, 2015 University Health Network news release on EurekAlert, which originated the news item, describes the laboratory research on mice,

In the lab in pre-clinical experiments, the team used low-frequency ultrasound to burst the porphyrin containing bubbles and observed that they fragmented into nanoparticles. Most importantly, the nanoparticles stayed within the tumour and could be tracked using imaging.

“Our work provides the first evidence that the microbubble reforms into nanoparticles after bursting and that it also retains its intrinsic imaging properties. We have identified a new mechanism for the delivery of nanoparticles to tumours, potentially overcoming one of the biggest translational challenges of cancer nanotechnology. In addition, we have demonstrated that imaging can be used to validate and track the delivery mechanism,” says Dr. Zheng, Senior Scientist at the Princess Margaret and also Professor of Medical Biophysics at the University of Toronto.

Conventional microbubbles, on the other hand, lose all intrinsic imaging and therapeutic properties once they burst, he says, in a blink-of-an-eye process that takes only a minute or so after bubbles are infused into the bloodstream.

“So for clinicians, harnessing microbubble to nanoparticle conversion may be a powerful new tool that enhances drug delivery to tumours, prolongs tumour visualization and enables them to treat cancerous tumours with greater precision.”

For the past decade, Dr. Zheng’s research focus has been on finding novel ways to use heat, light and sound to advance multi-modality imaging and create unique, organic nanoparticle delivery platforms capable of transporting cancer therapeutics directly to tumours.

Interesting development, although I suspect there are many challenges yet to be met such as ensuring the microbubbles consistently arrive at their intended destination in sufficient mass to be effective both for imaging purposes and, later, as nanoparticles for drug delivery purposes.

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

In situ conversion of porphyrin microbubbles to nanoparticles for multimodality imaging by Elizabeth Huynh, Ben Y. C. Leung, Brandon L. Helfield, Mojdeh Shakiba, Julie-Anne Gandier, Cheng S. Jin, Emma R. Master, Brian C. Wilson, David E. Goertz, & Gang Zheng. Nature Nanotechnology (2015) doi:10.1038/nnano.2015.25 Published online 30 March 2015

This paper is behind a paywall but a free preview is available via ReadCube Access.

This is one of those times where I’m including the funding agencies and the ‘About’ portions of the news release,

The research published today was funded by the Canadian Institutes of Health Research (CIHR) Frederick Banting and Charles Best Canada Graduate Scholarship, the Emerging Team Grant on Regenerative Medicine and Nanomedicine co-funded by the CIHR and the Canadian Space Agency, the Natural Sciences and Engineering Research Council of Canada, the Ontario Institute for Cancer Research, the International Collaborative R&D Project of the Ministry of Knowledge Economy, South Korea, the Joey and Toby Tanenbaum/Brazilian Ball Chair in Prostate Cancer Research, the Canada Foundation for Innovation and The Princess Margaret Cancer Foundation.

About Princess Margaret Cancer Centre, University Health Network

The Princess Margaret Cancer Centre has achieved an international reputation as a global leader in the fight against cancer and delivering personalized cancer medicine. The Princess Margaret, one of the top five international cancer research centres, is a member of the University Health Network, which also includes Toronto General Hospital, Toronto Western Hospital and Toronto Rehabilitation Institute. All are research hospitals affiliated with the University of Toronto. For more information, go to http://www.theprincessmargaret.ca or http://www.uhn.ca .

I was not expecting to see South Korea or Brazil mentioned in the funding. Generally, when multiple countries are funding research, their own research institutions are also involved. As for the Princess Margaret Cancer Centre being one of the top five such centres internationally, I wonder how these rankings are determined.

Gold nanotubes could be used in cancer therapies

Where nanotubes are concerned I don’t often see mention of any type other than ‘carbon’ nanotubes so, this Feb. 12, 2015 nanomedicine news item on ScienceDaily featuring ‘gold’ nanotubes caught my attention,

Scientists have shown that gold nanotubes have many applications in fighting cancer: internal nanoprobes for high-resolution imaging; drug delivery vehicles; and agents for destroying cancer cells.

The study, published today in the journal Advanced Functional Materials, details the first successful demonstration of the biomedical use of gold nanotubes in a mouse model of human cancer.

A Feb. 13, 2015 University of Leeds press release, which originated the news item despite what the publication date suggests, describes the research in more detail (Note: Links have been removed),

Study lead author Dr Sunjie Ye, who is based in both the School of Physics and Astronomy and the Leeds Institute for Biomedical and Clinical Sciences at the University of Leeds, said:  “High recurrence rates of tumours after surgical removal remain a formidable challenge in cancer therapy. Chemo- or radiotherapy is often given following surgery to prevent this, but these treatments cause serious side effects.

Gold nanotubes – that is, gold nanoparticles with tubular structures that resemble tiny drinking straws – have the potential to enhance the efficacy of these conventional treatments by integrating diagnosis and therapy in one single system.”

The researchers say that a new technique to control the length of nanotubes underpins the research. By controlling the length, the researchers were able to produce gold nanotubes with the right dimensions to absorb a type of light called ‘near infrared’.

The study’s corresponding author Professor Steve Evans, from the School of Physics and Astronomy at the University of Leeds, said: “Human tissue is transparent for certain frequencies of light – in the red/infrared region. This is why parts of your hand appear red when a torch is shone through it.

“When the gold nanotubes travel through the body, if light of the right frequency is shone on them they absorb the light. This light energy is converted to heat, rather like the warmth generated by the Sun on skin. Using a pulsed laser beam, we were able to rapidly raise the temperature in the vicinity of the nanotubes so that it was high enough to destroy cancer cells.”

In cell-based studies, by adjusting the brightness of the laser pulse, the researchers say they were able to control whether the gold nanotubes were in cancer-destruction mode, or ready to image tumours.

In order to see the gold nanotubes in the body, the researchers used a new type of  imaging technique called ‘multispectral optoacoustic tomography’ (MSOT) to detect the gold nanotubes in mice, in which gold nanotubes had been injected intravenously. It is the first biomedical application of gold nanotubes within a living organism. It was also shown that gold nanotubes were excreted from the body and therefore are unlikely to cause problems in terms of toxicity, an important consideration when developing nanoparticles for clinical use.

Study co-author Dr James McLaughlan, from the School of Electronic & Electrical Engineering at the University of Leeds, said: “This is the first demonstration of the production, and use for imaging and cancer therapy, of gold nanotubes that strongly absorb light within the ‘optical window’ of biological tissue.

“The nanotubes can be tumour-targeted and have a central ‘hollow’ core that can be loaded with a therapeutic payload. This combination of targeting and localised release of a therapeutic agent could, in this age of personalised medicine, be used to identify and treat cancer with minimal toxicity to patients.”

The use of gold nanotubes in imaging and other biomedical applications is currently progressing through trial stages towards early clinical studies.

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

Engineering Gold Nanotubes with Controlled Length and Near-Infrared Absorption for Theranostic Applications by Sunjie Ye, Gemma Marston, James R. McLaughlan, Daniel O. Sigle, Nicola Ingram, Steven Freear, Jeremy J. Baumberg, Richard J. Bushby, Alexander F. Markham, Kevin Critchley, Patricia Louise Coletta, and Stephen D. Evans. Advanced Functional Materials DOI: 10.1002/adfm.201404358 Article first published online: 12 FEB 2015

© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.

Doctor to patient: “Where would you like your carbon nanotubes implanted?”

A Nov. 3, 2013 news item on ScienceDaily offers some context, as well as, details for a sensing research project with medical applications being conducted at the Massachusetts Institute of Technology (MIT),

Nitric oxide (NO) is one of the most important signaling molecules in living cells, carrying messages within the brain and coordinating immune system functions. In many cancerous cells, levels are perturbed, but very little is known about how NO behaves in both healthy and cancerous cells.

“Nitric oxide has contradictory roles in cancer progression, and we need new tools in order to better understand it,” says Michael Strano, the Carbon P. Dubbs Professor of Chemical Engineering at MIT. “Our work provides a new tool for measuring this important molecule, and potentially others, in the body itself and in real time.”

Led by postdoc Nicole Iverson, Strano’s lab has built a sensor that can monitor NO in living animals for more than a year. The sensors, described in the Nov. 3 issue of Nature Nanotechnology, can be implanted under the skin and used to monitor inflammation — a process that produces NO. This is the first demonstration that nanosensors could be used within the body for this extended period of time.

The Nov. 3, 2013 MIT news release (also on EurekAlert) written by Anne Trafton, which originated the news item, describes carbon nanotubes and how they are being used as sensing devices by the research team,

Carbon nanotubes — hollow, one-nanometer-thick cylinders made of pure carbon — have drawn great interest as sensors. Strano’s lab has recently developed carbon nanotube sensors for a variety of molecules, including hydrogen peroxide and toxic agents such as the nerve gas sarin. Such sensors take advantage of carbon nanotubes’ natural fluorescence, by coupling them to a molecule that binds to a specific target. When the target is bound, the tubes’ fluorescence brightens or dims.

Strano’s lab has previously shown that carbon nanotubes can detect NO if the tubes are wrapped in DNA with a particular sequence. In the new paper, the researchers modified the nanotubes to create two different types of sensors: one that can be injected into the bloodstream for short-term monitoring, and another that is embedded in a gel so it can be implanted long-term under the skin.

To make the particles injectable, Iverson attached PEG, a biocompatible polymer that inhibits particle-clumping in the bloodstream. She found that when injected into mice, the particles can flow through the lungs and heart without causing any damage. Most of the particles accumulate in the liver, where they can be used to monitor NO associated with inflammation.

“So far we have only looked at the liver, but we do see that it stays in the bloodstream and goes to kidneys. Potentially we could study all different areas of the body with this injectable nanoparticle,” Iverson says.

The longer-term sensor consists of nanotubes embedded in a gel made from alginate, a polymer found in algae. Once this gel is implanted under the skin of the mice, it stays in place and remains functional for 400 days; the researchers believe it could last even longer. This kind of sensor could be used to monitor cancer or other inflammatory diseases, or to detect immune reactions in patients with artificial hips or other implanted devices, according to the researchers.

Once the sensors are in the body, the researchers shine a near-infrared laser on them, producing a near-infrared fluorescent signal that can be read using an instrument that can tell the difference between nanotubes and other background fluorescence.

There is research into how the sensor could be adapted for use in diabetics, from the news release,

Iverson is now working on adapting the technology to detect glucose, by wrapping different kinds of molecules around the nanotubes.

Most diabetic patients must prick their fingers several times a day to take blood glucose readings. While there are electrochemical glucose sensors available that can be attached to the skin, those sensors last only a week at most, and there is a risk of infection because the electrode pierces the skin.

Furthermore, Strano says, the electrochemical sensor technology is not accurate enough to be incorporated into the kind of closed-loop monitoring system that scientists are now working toward. This type of system would consist of a sensor that offers real-time glucose monitoring, connected to an insulin pump that would deliver insulin when needed, with no need for finger pricking or insulin injection by the patient.

“The current thinking is that every part of the closed-loop system is in place except for an accurate and stable sensor. There is considerable opportunity to improve upon devices that are now on the market so that a complete system can be realized,” Strano says.

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

In vivo biosensing via tissue-localizable near-infrared-fluorescent single-walled carbon nanotubes by Nicole M. Iverson, Paul W. Barone, Mia Shandell, Laura J. Trudel, Selda Sen, Fatih Sen, Vsevolod Ivanov, Esha Atolia, Edgardo Farias, Thomas P. McNicholas, Nigel Reuel, Nicola M. A. Parry, Gerald N. Wogan & Michael S. Strano. Nature Nanotechnology (2013) doi:10.1038/nnano.2013.222 Published online 03 November 2013

There is a free preview of the article available via ReadCube Access otherwise this article is behind a paywall.

How many Holy Grails are there? Nanoscientists have reached another one (cancer, again)

A July 24, 2013 news item on ScienceDaily mentions the latest ‘Holy Grail’ breakthrough’,

Just months after setting a record for detecting the smallest single virus in solution, researchers at the Polytechnic Institute of New York University (NYU-Poly) have announced a new breakthrough: They used a nano-enhanced version of their patented microcavity biosensor to detect a single cancer marker protein, which is one-sixth the size of the smallest virus, and even smaller molecules below the mass of all known markers.

The July 24, 2013 Polytechnic Institute of New York University (NYU-Poly) press release features the Holy Grail in its headline (Note: Links have been removed),

NYU-Poly Nano Scientists Reach the Holy Grail in Label-Free Cancer Marker Detection: Single Molecules

Unlike current technology, which attaches a fluorescent molecule, or label, to the antigen to allow it to be seen, the new process detects the antigen without an interfering label.
Stephen Arnold, university professor of applied physics and member of the Othmer-Jacobs Department of Chemical and Biomolecular Engineering, published details of the achievement in Nano Letters, a publication of the American Chemical Society.

The press release goes on to the describe the context for this breakthrough and provides details about it (Note: A link has been removed),

In 2012, Arnold and his team were able to detect in solution the smallest known RNA virus, MS2, with a mass of 6 attograms. Now, with experimental work by postdoctoral fellow Venkata Dantham and former student David Keng, two proteins have been detected: a human cancer marker protein called Thyroglobulin, with a mass of just 1 attogram, and the bovine form of a common plasma protein, serum albumin, with a far smaller mass of 0.11 attogram. [emphasis mine] “An attogram is a millionth of a millionth of a millionth of a gram,” said Arnold, “and we believe that our new limit of detection may be smaller than 0.01 attogram.”

This latest milestone builds on a technique pioneered by Arnold and collaborators from NYU-Poly and Fordham University.  In 2012, the researchers set the first sizing record by treating a novel biosensor with plasmonic gold nano-receptors, enhancing the electric field of the sensor and allowing even the smallest shifts in resonant frequency to be detected. Their plan was to design a medical diagnostic device capable of identifying a single virus particle in a point-of-care setting, without the use of special assay preparations.

At the time, the notion of detecting a single protein—phenomenally smaller than a virus—was set forth as the ultimate goal.

“Proteins run the body,” explained Arnold. “When the immune system encounters virus, it pumps out huge quantities of antibody proteins, and all cancers generate protein markers. A test capable of detecting a single protein would be the most sensitive diagnostic test imaginable.”

To the surprise of the researchers, examination of their nanoreceptor under a transmission electron microscope revealed that its gold shell surface was covered with random bumps roughly the size of a protein. Computer mapping and simulations created by Stephen Holler, once Arnold’s student and now assistant professor of physics at Fordham University, showed that these irregularities generate their own highly reactive local sensitivity field extending out several nanometers, amplifying the capabilities of the sensor far beyond original predictions. “A virus is far too large to be aided in detection by this field,” Arnold said. “Proteins are just a few nanometers across—exactly the right size to register in this space.”

The implications of single protein detection are significant and may lay the foundation for improved medical therapeutics.  Among other advances, Arnold and his colleagues posit that the ability to follow a signal in real time—to actually witness the detection of a single disease marker protein and track its movement—may yield new understanding of how proteins attach to antibodies.

Arnold named the novel method of label-free detection “whispering gallery-mode biosensing” because light waves in the system reminded him of the way that voices bounce around the whispering gallery under the dome of St. Paul’s Cathedral in London. A laser sends light through a glass fiber to a detector. When a microsphere is placed against the fiber, certain wavelengths of light detour into the sphere and bounce around inside, creating a dip in the light that the detector receives. When a molecule like a cancer marker clings to a gold nanoshell attached to the microsphere, the microsphere’s resonant frequency shifts by a measureable amount.

Just a brief comment about the attogram, this is the first time I’ve seen atto prepended to anything other than a unit of time, e.g. attosecond. For anyone who’s not familiar with the atto scale, it’s less than femto,which is less than pico, which is less than nano. There are two more scales moving downward after atto:  zetto followed by yocto. As far as I’m aware, yocto is still the smallest unit of measurement. (more simply and moving down in scale: micro, nano, pico, femto, atto, zetto, yocto)

Back to the Holy Grail at hand, here’s a link to and a citation for the published paper,

Label-Free Detection of Single Protein Using a Nanoplasmonic-Photonic Hybrid Microcavity by Venkata R. Dantham, Stephen Holler, Curtis Barbre, David Keng, Vasily Kolchenko, and Stephen Arnold. Nano Lett., 2013, 13 (7), pp 3347–3351 DOI: 10.1021/nl401633y Publication Date (Web): June 18, 2013
Copyright © 2013 American Chemical Society

This paper is behind a paywall.

Multi-walled carbon nanotubes, cancer, and the US National Institute of Occupational Health and Safety’s (NIOSH) latest findings

A Mar. 11, 2013 news item on Nanowerk reveals some of the latest research performed by US National Institute of Occupational Health Safety (NIOSH) researchers into the question of whether or not multi-walled carbon nanotubes (MWCNT) cause cancer,

Earlier today, at the annual meeting of the Society of Toxicology, NIOSH researchers reported preliminary findings from a new laboratory study in which mice were exposed by inhalation to multi-walled carbon nanotubes (MWCNT). The study was designed to investigate whether these tiny particles have potential to initiate or promote cancer. By “initiate,” we mean the ability of a substance to cause mutations in DNA that can lead to tumors. By “promote,” we mean the ability of a substance to cause cells that have already sustained such DNA mutations to then become tumors.

It is very important to have new data that describe the potential health hazards that these materials might represent, so that protective measures can be developed to ensure the safe advancement of nanotechnology in the many industries where it is being applied.

The Mar. 11, 2013 posting (which originated the news item) by Vincent Castranova, PhD; Charles L Geraci, PhD; Paul Schulte, PhD  on the NIOSH blog provides details about the experimental protocols and the outcome of the experiments,

In the NIOSH study, a group of laboratory mice were injected with a chemical that is a known cancer initiator, methylcholanthrene.  Another group of mice were injected with a saline solution as a control group.  The mice then were exposed by inhalation either to air or to a concentration of MWCNT.   These protocols enabled the researchers to investigate whether MWNCT alone would initiate cancer in mice, or whether MWCNT would promote cancer where the initiator, methylcholanthrene, had already been applied.

Mice receiving both the initiator chemical plus exposure to MWCNT were significantly more likely to develop tumors (90% incidence) and have more tumors (an average of 3.3 tumors/mouse lung) than mice receiving the initiator chemical alone (50% of mice developing tumors with an average of 1.4 tumors/lung).  Additionally, mice exposed to MWCNT and to MWCNT plus the initiator chemical had larger tumors than the respective control groups.  The number of tumors per animal exposed to MWCNT alone was not significantly elevated compared with the number per animal in the controls.  These results indicate that MWCNT can increase the risk of cancer in mice exposed to a known carcinogen.  The study does not suggest that MWCNTs alone cause cancer in mice.

That last sentence is quite important because (from the NIOSH blog post),

Several earlier studies in the scientific literature indicated that MWCNT could have the potential to initiate or promote cancer. The new NIOSH study is the first to show that MWCNT is a cancer promoter in a laboratory experiment, and reports the growth of lung tumors in laboratory mice following inhalation exposure to MWCNT rather than injection, instillation, or aspiration.  Inhalation exposure most closely resembles the exposure route of greatest concern in the workplace. In the study, laboratory mice were exposed to one type of MWCNT through inhalation at a concentration of 5 milligrams per cubic meter of air for five hours per day for a period of 15 days.

Risk of occupational cancer depends on the potency of a given substance to cause or promote cancer and the concentration and duration of worker exposure to that substance.  This research is an important step in our understanding of the hazard associated with MWCNT, but before we can determine whether MWCNT pose an occupational cancer risk, we need more information about actual exposure levels and the types and nature of MWCNT being used in the workplace, and how that compares to the material  used in this study.

This study is part of a larger program designed to establish safety practices with regard to handling nanomaterials/nanoparticles (from the NIOSH blog post),

These laboratory studies are part of a strategic program of NIOSH research to better understand the occupational health and safety implications of nanoparticle exposure, and to make authoritative science-based recommendations for controlling exposures so that the technology is developed responsibly as the research advances, and the societal benefits of nanotechnology can be realized.  NIOSH has worked closely with diverse public and private sector partners over the past decade to incorporate occupational health and safety into practical strategies for safe development of this revolutionary technology. More information is available on the NIOSH nanotechnology topic page.

There is no mention in the blog post as to whether the MWCNTs in this latest work were long or short or a mixture of both. Unfortunately, the study has not yet been published in a journal, so it’s not yet available for reading purposes. I did mention carbon nanotubes and toxicity in a Jan. 16, 2013 posting about a recent study,

Researchers at the University College of London (UCL), France’s Centre national de la recherche scientifique (CNRS), and Italy’s University of Trieste have determined that carbon nanotube toxicity issues can be addressed be reducing their length and treating them chemically.

While I find this latest work from NIOSH interesting, it’s hard for me to understand why there’s no mention of length. Unless, the NIOSH work is focused on what happens when MWCNTs are inhaled along with known cancer initiators and they believe that length is not a factor.

ETA Mar. 15, 2013: I did find get some information about the length (long carbon nanotubes for the most part) as per this Mar. 14, 2013 posting or you can find the update in my Mar. 15, 2013 posting here.

University of Alberta, Movember, and nanomedicine cancer research

Not sure when November became Movember but in keeping with the theme researchers at the University of Alberta have just published their work on developing ‘homing beacon drugs’ that eliminate cancerous cells only while leaving healthy cells to go about their work. From the Nov. 20, 2012 University of Alberta news release by Raquel Maurier (Note: I have removed some links),

A medical researcher with the University of Alberta and his team just published their findings about their work on developing “homing beacon drugs” that kill only cancer cells, not healthy ones, thanks to nanotechnology.

John Lewis, the Sojonky Chair in Prostate Cancer Research with the Faculty of Medicine & Dentistry, published his findings in the peer-reviewed journal, Nano Letters. He is also an associate professor in the Department of Oncology at the U of A, the director of the Translational Prostate Cancer Research Group and a fellow of the National Institute for Nanotechnology.

Lewis noted chemotherapy goes through the body and kills any cells that are dividing, even healthy ones—which is why cancer patients have immune-system problems, hair loss, nausea and skin problems.

“We are developing smart drugs that determine which are the cancer cells and which aren’t, then selectively kill only the cancer cells. The drugs look for a protein that is only found in cancer cells, not normal cells. This system acts like a homing beacon for tumours.”

These drugs, tested to date in only animal lab models, could be used within a week of cancer diagnoses, predicts Lewis. The drugs would target cancerous cells throughout the body, attacking sneaky cancer cells that have already escaped and grown outside the site of the main tumour.

Lewis isn’t sure when these homing beacon drugs could be available for physicians to use with patients, but hopes his works paves the way for patient-centred therapies.

Catherine Griwkowsky posted a Nov. 20, 2012 article and video about the research on the Edmonton Sun website which features an interview with the lead researcher, Choi-Fong Cho,

Fong Cho, lead researcher on the study published in the peer-reviewed Nano Letters, said the nanoparticles can be used both for imaging and for drug delivery.

“For my purpose, you put in something that binds to your cancer directly to a particle that leads to your cancer and the nanoparticle will light up the cancer,” she said.

“You could also, for example, put drugs on it and deliver the drugs specifically to the tumour without harming the surrounding cells and tissues that causes a lot of side effects.”

The lab is also looking at ways of identifying and stopping metastasis …

In keeping with the Movember theme, here’s John Lewis,

UAlberta medical researcher John Lewis sports a Movember mustache to support prostate cancer awareness and research. Lewis and his team are developing ‘homing beacon drugs’ that can target cancer cells while sparing healthy cells. Their findings could help improve survival rates and quality of life for people undergoing cancer treatment. (downloaded from http://www.news.ualberta.ca/article.aspx?id=4CD917F418E3492F92CCCDDA7B8221640)

Here’s a citation for Cho’s and Lewis’ article,

Discovery of Novel Integrin Ligands from Combinatorial Libraries Using a Multiplex “Beads on a Bead” Approach by Choi-Fong Cho, Giulio A. Amadei, Daniel Breadner, Leonard G. Luyt, and John D. Lewis in Nano Lett., 2012, 12 (11), pp 5957–5965 DOI: 10.1021/nl3034043 Publication Date (Web): October 25, 2012 Copyright © 2012 American Chemical Society

This article is behind a paywall.

Nanodiagnostics: a roundtable at Kavli and new report from Cientifica

The Kavli Foundation, based in California, held a roundtable discussion on ‘Fighting Cancer with Nanotechnology‘ which focused largely on diagnostics and drug delivery. According to a March 14, 2012 news item on Nanowerk, the four participants were:

  • Anna Barker – Former Deputy Director of the National Cancer Institute (NCI) and current Director of Arizona State University’s Transformative Healthcare Networks;
  • Mark E. Davis – Professor of Chemical Engineering at the California Institute of Technology (Caltech), and a member of the Experimental Therapeutics Program of the Comprehensive Cancer Center at the City of Hope;
  • James Heath – Professor of Chemistry at Caltech and a founding Board member of Caltech’s Kavli Nanoscience Institute;
  • Michael Phelps – Norton Simon Professor, and Chair of Molecular and Medical Pharmacology at the University of California Los Angeles.

The researchers discussed how nanotechnology holds the promise of revolutionizing the way medicine wages war against cancer, from providing new ways to combine drugs to delivering gene-silencing therapeutics for cancer cells. [emphasis mine]

Yet again, war has been used as a metaphor for healing. I particularly appreciate the way ‘revolution’, which resonates with US audiences in a very particular way, has been introduced.

The discussion features diagnostics,

JAMES HEATH: That is certainly an important application. A typical diagnostic test measures only a single protein. But the nature of cancer—even a single cancer type—is that it can vary significantly from patient to patient. The implication is that there is probably not a single protein biomarker that can distinguish between such patient variations. Even to confidently address a single diagnostic question may take measuring several protein biomarkers. Discovering the right biomarkers is extremely challenging—you might have 300 candidate biomarkers from which you want to choose just six, but you will likely have to test all 300 on a very large patient pool to determine the best six. That’s tough to do with existing technologies because each protein measurement requires a large sample of blood or tumor tissue, and each measurement is time-consuming, labor intensive and expensive. With some of the emerging nanotechnologies, a large panel of candidate protein biomarkers can be rapidly measured from just a pinprick of blood, or a tissue sample as small as a single cell. This allows one to accelerate the development of conventional diagnostic tests, but it also opens up the possibilities for fundamentally new diagnostic approaches. These are opportunities that nanotech is bringing into play that simply weren’t there before.

Here’s one of my favourite comments,

MICHAEL PHELPS: Yes. All of us developing therapeutics want to have a transparent patient—to see where the drug goes throughout all tissues of the body, whether it hits the disease target in a sufficient dose to induce the desired therapeutic effect on the target, and where else the drug goes in the body regarding side effects. [emphasis mine] PET [positron emission tomography ‘scan’] can reveal all this. For this reason almost all drug companies now use PET in their discovery and development processes.

I suspect Phelps was a bit over enthused and spoke without thinking. I’m sure most doctors and researchers would agree that what they want is to heal without harm and not transparent patients. That’s why they’re so excited about nanotechnology and therapeutics, they’re trying to eliminate or, at least, lessen harm in the healing process. It would be nice though if they get past the ‘war’ metaphors and dreams of transparent patients.

I found the comments about the US FDA (Food and Drug Administration), pharmaceutical companies and biotech startups quite interesting,

ANNA BARKER: These challenges are mostly related to perception and having the tools to demonstrate that the agent does what you say it does. It’s more difficult for nanotherapeutics than for other drugs because they employ a new set of technologies that the FDA is more guarded about approving. The FDA is responsible for the health of the American public, so they are very careful about putting anything new into the population. So the challenges have to do with showing you can deliver what you said you were going to deliver to the target, and that the toxicity and distribution of the agent in the body is what you predicted. You have to have different measures than what is included in the classic toxicology testing packages we use for potential drugs.

MARK DAVIS: There’s so much cool science that people want to do, but you’re limited in what you can do in patients for a number of reasons. One is financial. This area is not being pushed forward by big Pharma, but by biotech companies, and they have limited resources. Secondly, the FDA is still learning about these innovations, they can limit what you are allowed to do in a clinical trial. For example, when we did the first clinical trial with a nanoparticle that had a targeting agent enabling it to latch onto a specific receptor on cancer cells and a gene silencing payload, we realized it would be important to know if patients have this receptor and the gene target of the payload to begin with. Prebiopsies from patients before testing the nanotherapeutic on them to see if the tumor cells had this receptor and gene target in abundance would have been helpful. However, in this first-in-man trial, the FDA did not allow required biopsies, and they were performed on a volunteer-basis only.

It is a fascinating discussion as it provides insight into the field of nanotherapeutics and into the some of the researchers.

On the topic of nanodiagnostics but this time focusing on the business end of things, a new report has been released by Cientifica. From the March 13, 2012 press release,

Nanodiagnostics will be a $50-billion market by 2021; Cientifica’s “Nanotechnology for Medical Diagnostics” looks at emerging nanoscale technologies

Following on from Cientifica’s Nanotechnology for Drug Delivery report series, “Nanotechnology for Medical Diagnostics,” a 237-page report, takes a comprehensive look at current and emerging nanoscale technologies used for medical diagnostics.

Areas examined include quantum dots, gold nanoparticles, exosomes, nanoporous silica, nanowires, micro- and nanocantilever arrays, carbon nanotubes, ion channel switch nanobiosensors, and many more.

Cientifica estimates medical imaging is the sector showing the highest growth and impact of nanomaterials. Already a $1.7-billion market, with gold nanoparticle applications accounting for $959 million, imaging will continue to be the largest nanodiagnostics sector, with gold nanoparticles, quantum dots and nanobiosensors all easily exceeding $10 billion.

“Getting onboard with the right technology at the right time is crucial,” said Harper [Tim Harper, Cientifica’s Chief Executive Officer]. “The use of exosomes in diagnosis, for instance, a relatively new technique and a tiny market, is set to reach close to half a billion dollars by 2021.”

You can find out more and/or purchase the report here.

I have written about Cientifica’s  Nanotechnology for Drug Delivery (NDD) white paper here and have published an interview with Tim Harper about global nanotechnology funding and economic impacts here.

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.

Bacteria, pyramids, cancer, and Sylvain Martel

Canada’s national newspaper (as they like to bill themselves), the Globe and Mail featured Québec researcher’s (Sylvain Martel) work in a Dec. 13, 2011 article by Bertrand Marotte. From the news article,

Professor Sylvain Martel is already a world leader in the field of nano-robotics, but now he’s working to make a medical dream reality: To deliver toxic drug treatments directly to cancerous cells without damaging the body’s healthy tissue.

I have profiled Martel’s work before in an April 6 2010 posting about bacterial nanobots (amongst other subjects) and in a March 16, 2011 posting about his work with remote-controlled microcarriers.

It seems that his next project will combine the work on bacteria and microcarriers (from the Globe and Mail article),

Bolstered by his recent success in guiding micro-carriers loaded with cancer-fighting medications into a rabbit’s liver, he and his team of up to 20 researchers from several disciplines are working to transfer the method to the treatment of colorectal cancer in humans within four years.

This time around he is not using micro-carriers to deliver the drug to the tumour, but rather bacteria.

Here’s a video of the bacteria which illustrates Martel’s earlier success with ‘training’ them to build a pyramid.

The latest breakthrough reported in March 2011 (from my posting) implemented an MRI (magnetic resonance imaging) machine,

Known for being the world’s first researcher to have guided a magnetic sphere through a living artery, Professor Martel is announcing a spectacular new breakthrough in the field of nanomedicine. Using a magnetic resonance imaging (MRI) system, his team successfully guided microcarriers loaded with a dose of anti-cancer drug through the bloodstream of a living rabbit, right up to a targeted area in the liver, where the drug was successfully administered. This is a medical first that will help improve chemoembolization, a current treatment for liver cancer.

Here’s what Martel is trying to accomplish now (from the Globe and Mail article),

The MRI machine’s magnetic field is manipulated by [a] sophisticated software program that helps guide the magnetically sensitive bacteria to the tumour mass.

Attached to the bacteria is a capsule containing the cancer-fighting drug. The bacteria are tricked into swimming to an artificially created “magnetic north” at the centre of the tumour, where they will die off after 30 to 40 minutes. The micro-mules, however, have left their precious cargo: the capsule, whose envelope breaks and releases the drug.

I’m not entirely sure why the drug won’t destroy health tissue after it’s finished with the tumour but that detail is not offered in Marotte’s story which, in the last few paragraphs, switches focus from medical breakthroughs to the importance of venture capital funding for Canadian biotech research.

I wish Martel and his team great success.

Bot bot here and bot bot there and a bot bot everywhere but not Old Macdonald’s Farm

The Materials Research Society (MRS) has a Fall 2011 meeting in Boston, Massachusetts scheduled for Nov. 28, 2011 to Dec. 2, 2011, which will feature amongst other exhibits,  ‘mibots’. From the Nov. 9, 2011 news item on Azonano,

…  new “miBots” from Imina Technologies (Ecublens, Switzerland).

.. are more than nanomanipulators. Unlike conventional systems, they are virtually untethered and move independently. Working individually or in groups, they can be fitted with a variety of tools such as grippers, probes, and optical fibers so that, in addition to manipulating the sample, they can illuminate a nano workspace and conduct force or electrical measurements. Vacuum ready, miBots’ proprietary monolithic structure makes them robust, mechanically and thermally stable, and less sensitive to vibration.

Imina Technologies has engineered a variety of stage options for these novel mini robots. For conventional installation on inverted light microscopes (LM), SEMs, or focused-ion beam systems (FIBs), the “miBase” provides control and maneuvering room for up to four miBots. Special apertures accommodate illumination for the LM and stubs for SEMs, and multiple coaxial I/O connections enable electrical characterization and testing.

You can find out more about Imina Technologies and their ‘mibots’ here.

For a completely different kind of bot, a company named Nanobotmodels, situated in the Ukraine, offers illustration, animations, and presentation materials. From the company’s About page,

Our company Nanobotmodels was founded in 2007 and its goal is todevelop modern art-science-technology intersections. Nanotechnology boosts medicine, engineering, biotechnology, electronics soon, so artwork and vision of the nanofuture will be very useful.

We are making hi-end nanotechnology and nanomedicine illustration and animation. You can imagine any interesting-to-you animation, illustration or presentation materials, and we can make them real.

The level of detail in each medical illustration can be used to simplify complex structures and make them visually attractive.

Our clients include the largest medicine photobanks, nanotechnology magazines and publications, educational organization, and private companies.

Company was founded by CEO Svidinenko Yuriy, futurist and nanotechnology artist.

Our team consists of modern artists, modelers and nanotechnology scientists.

Here’s a bit more about the company’s work in medical illustration from a Nov. 11, 2011 news item at Nanotechnology Now,

One heat therapy to destroy cancer tumors using nanoparticles is called AuroShell™. The AuroShell™ nanoparticles circulate through a patient’s bloodstream, exiting where the blood vessels are leaking at the site of cancer tumors. Once the nanoparticles accumulate at the tumor the AuroShell™ nanoparticles are used to concentrate the heat from infrared light to destroy cancer cells with minimal damage to surrounding healthy cells. Nanobotmodels company provides good visual illustration of this process. Nanospectra Biosciences has developed such a treatment using AuroShell™ that has been approved for a pilot trial with human patients.

Gold nanoparticles can absorb different frequencies of light, depending on their shape. Rod-shaped particles absorb light at near-infrared frequency; this light heats the rods but passes harmlessly through human tissue. Sphere-shaped nanoparticles absorb laser radiation and passes harmlessly through human tissue too.

Nanobotmodels Company provides visual illustration of nanoparticle cancer treatment. Our goal – make realistic vision of modern drug delivery technology.

I found this sample on the company’s website gallery,

Illustration from Nanobotmodels website: Nanomechanical robots attacking cancer cell

You can find more artwork here.

Those are all the bots for today.