Christine Peterson

Foresight Co-Founder and Past President Christine Peterson is interviewed on the Singularity Weblog in a 47-minute tour that covers nanotechnology, the founding of the Foresight Institute, her work on personal life extension through Health Activator, open source, and the Technological Singularity. “Christine Peterson on Singularity 1 on 1: Join Us to Push the Future in a Positive Direction“:

During my Singularity 1 on 1 interview with Christine Peterson we discuss a variety of topics such as: how she got interested in nanotechnology and the definition thereof; how, together with Eric Drexler, she started the Foresight Institute for Nanotechnology; her interest in life extension; Dr. Drexler’s seminal book Engines of Creation; cryonics and chemical brain preservation; 23andMe and other high- and low-tech tips for improved longevity; whether we should fear nanotechnology or not; the 3 most exciting promises of nanotech; women in technology; coining the term “open source” and using Apple computers; the technological singularity and her take on it…

Hear Christine discuss some challenges while presenting an essentially optimistic message—a wonderful future is coming from science and technology over the next few decades—a future that encourages everyone to get involved.
—James Lewis, PhD

Shanta Dhar, right, an assistant professor of chemistry in the UGA Franklin College of Arts and Sciences, and doctoral student Sean Marrache have fabricated nanoparticles that boost the effectiveness of drugs by delivering them to the mitochondria of cells (credit: University of Georgia).

Targeted drug delivery is one of the most important contributions of current and near-term nanotechnology to medicine. New research shows that specifically targeting one component of the cell makes nanoparticle-mediated drug delivery much more effective for a variety of applications. A hat tip to KurzweilAI.net for reprinting this University of Georgia news release “UGA researchers boost efficacy of drugs by using nanoparticles to target ‘powerhouse of cells’“:

Nanoparticles have shown great promise in the targeted delivery of drugs to cells, but researchers at the University of Georgia have refined the drug delivery process further by using nanoparticles to deliver drugs to a specific organelle within cells.

By targeting mitochondria, often called “the powerhouse of cells,” the researchers increased the effectiveness of mitochondria-acting therapeutics used to treat cancer, Alzheimer’s disease and obesity in studies conducted with cultured cells.

“The mitochondrion is a complex organelle that is very difficult to reach, but these nanoparticles are engineered so that they do the right job in the right place,” said senior author Shanta Dhar, an assistant professor of chemistry in the UGA Franklin College of Arts and Sciences.

Dhar and her co-author, doctoral student Sean Marrache, used a biodegradable, FDA-approved polymer to fabricate their nanoparticles and then used the particles to encapsulate and test drugs that treat a variety of conditions. Their results were published this week in early edition of the journal Proceedings of the National Academy of Sciences [abstract].

To test the effectiveness of their drug targeting system against cancer, they encapsulated the drug lonidamine, which works by inhibiting energy production in the mitochondria, and, separately, a form of the antioxidant vitamin E. They then treated cultured cancer cells and found that mitochondrial targeting increased the effectiveness of the drugs by more than 100 times when compared to the drugs alone and by five times when compared to the delivery of drugs with nanoparticles that target the outside of cells.

Similarly, the compound curcumin has shown promise in inhibiting formation of the amyloid plaques that are a hallmark of Alzheimer’s disease, but it quickly degrades in the presence of light and is broken down rapidly by the body. By encapsulating curcumin in the mitochondria-targeting nanoparticles, however, the researchers were able to restore the ability of brain cells in culture to survive despite the presence of a compound that encourages plaque formation. Nearly 100 percent of the cells treated with the mitochondria-targeting nanoparticles survived in the presence of the plaque-inducing compound, compared to 67 percent of cells treated with free curcumin and 70 percent of cells treated with nanoparticles that target the outside of cells.

Finally, the researchers encapsulated the obesity drug 2,4-DNP—which works by making energy production in the mitochondria less efficient—in their nanoparticles and found that it reduced the production of fat by cultured cells known as preadipocytes by 67 percent compared to cells treated with the drug alone and by 61 percent of cells treated with nanoparticles that target the outside of cells.

“A lot of diseases are associated with dysfunctional mitochondria, but many of the drugs that act on the mitochondria can’t get there,” Marrache said. “Rather than try to alter the drugs, which can reduce their effectiveness, we encapsulate them in these nanoparticles and precisely deliver them to the mitochondria.”

Dhar said that getting drugs to the mitochondria is no simple feat. Upon entering cells, nanoparticles enter a sorting center known as the endosome. The first thing Dhar and Marrache had to demonstrate was that the nanoparticles escape from the endosome and don’t end up in the cells’ disposal center, the lysosome.

The mitochondria itself is protected by two membranes separated by an interstitial space. The outer membrane only permits molecules of a certain size to pass through, while the inner membrane only permits molecules of a given range of charges to pass. The researchers constructed a library of nanoparticles and tested them until they identified the optimum size range—64 to 80 nanometers, or approximately 1,000 times finer than the width of a human hair—and an optimum surface charge, plus 34 millivolts.

Dhar notes the components they used to create the nanoparticles are FDA approved and that their methods are highly reproducible and therefore have the potential to be translated into clinical settings. The researchers are currently testing their targeted delivery system in rodents and say that preliminary results are promising.

“Mitochondrial dysfunctions cause many disorders in humans,” Dhar said, ” so there are several potential applications for this delivery system.”

Subject to the usual caveat that these nanoparticles are still in an early stage of testing, having been tested only in cell culture, it is remarkable that such effective targeting to reach the matrix of the mitochondria was achieved by the relatively crude strategy of optimizing only particle size and surface charge through engineering polymer composition. So success was achieved through clever application of biological knowledge more than through sophisticated atomically precise construction. It will be fascinating to watch the evolution of this technology as ever more sophisticated construction leads to increasing effectiveness. While we are waiting, this targeting of drug delivery to mitochondria is likely to be especially helpful because so many pathologies seem rooted in imperfections and consequences of the symbiosis that led to eukaryotic cells, and all complex life on Earth, nearly two billion years ago.
—James Lewis, PhD

The shear-activated nanotherapeutic breaks apart and releases its drug when it encounters regions of vascular narrowing (credit: Wyss Institute).

A novel nanoparticle that aggregates under normal blood flow but breaks apart under high shear stress encountered in regions of vascular narrowing was found to improve survival in mice with occluded blood vessels with 1/50th of the normal dose of a standard clot-busting drug. A hat tip to KurzweilAI for describing this news release “Harvard’s Wyss Institute Develops Novel Nanotherapeutic that Delivers Clot-Busting Drugs Directly to Obstructed Blood Vessels“:

Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University have developed a novel biomimetic strategy that delivers life-saving nanotherapeutics directly to obstructed blood vessels, dissolving blood clots before they cause serious damage or even death. This new approach enables thrombus dissolution while using only a fraction of the drug dose normally required, thereby minimizing bleeding side effects that currently limit widespread use of clot-busting drugs.

The research findings, which were published online today in the journal Science [abstract], have significant implications for treating major causes of death, such as heart attack, stroke and pulmonary embolism, that are caused by acute vascular blockage by blood thrombi.

The inspiration for the targeted vascular nanotherapeutic approach came from the way in which normal blood platelets rapidly adhere to the lining of narrowed vessels, contributing to the development of atherosclerotic plaques. When vessels narrow, high shear stresses provide a physical cue for circulating platelets to stick to the vessel wall selectively in these regions. The vascular nanotherapeutic is similarly about the size of a platelet, but it is an aggregate of biodegradable nanoparticles that have been coated with the clot-busting drug, tissue plasminogen activator (tPA). Much like when a wet ball of sand breaks up into individual grains when it is sheared between two hands, the aggregates selectively dissociate and release tPA-coated nanoparticles that bind to clots and degrade them when they sense high shear stress in regions of vascular narrowing, such as caused by blood clot formation.

Disruption of normal blood flow to the heart, lung, and brain due to thrombosis is one of the leading causes of death and long-term adult disability in the developing world. Today, patients with pulmonary embolism, strokes, heart attacks and other types of acute thrombosis leading to near-complete vascular occlusion, are most frequently treated in an acute care hospital setting using systemic dosages of powerful clot-dissolving drugs. Because these drugs can cause severe and often fatal bleeding as they circulate freely throughout the body, the size of the dosage given to any patient is limited because efficacy must be balanced against risk.

The new shear-activated nanotherapeutic has the potential to overcome these efficacy limitations. By targeting and concentrating drug at the precise site of the blood vessel obstruction, the Wyss team has been able to achieve improved survival in mice with occluded lung vessels with less than 1/50th of the normal therapeutic dose, which should translate into fewer side effects and greater safety. This raises the possibility that, in the future, an emergency technician might be able immediately administer this nanotherapeutic to anyone suspected of having a life-threatening blood clot in a vital organ before the patient even reached the hospital.

This work is yet another instance in which near-term nanotechnology is providing opportunities to make current therapeutic approaches (biotech clot busting drugs, like tissue plasminogen activator) more effective and much safer to use so that they can be used more widely, supplied quickly in emergency situations, and, we can hope, help many more people.
—James Lewis, PhD

Princeton researchers dramatically improved the sensitivity of immunoassays, a common medical test, using the nanomaterial shown here. The material consists of a series of glass pillars in a layer of gold. Each pillar is speckled on its sides with gold dots and capped with a gold disk. Each pillar is just 60 nanometers in diameter, 1/1,000th the width of a human hair. (Credit: Stephen Chou/Analytical Chemistry)

Near-term nanotechnology will not only enrich medicine with new cures, but will contribute to greatly improving existing procedures. For example, a new nanomaterial has improved the sensitivity of a common medical test three million times. A hat tip to ScienceDaily for reprinting this Princeton University news release posted by Steven Schultz “Nanotechnology breakthrough could dramatically improve medical tests“:

A laboratory test used to detect disease and perform biological research could be made more than 3 million times more sensitive, according to researchers who combined standard biological tools with a breakthrough in nanotechnology.

The increased performance could greatly improve the early detection of cancer, Alzheimer’s disease and other disorders by allowing doctors to detect far lower concentrations of telltale markers than was previously practical.

The breakthrough involves a common biological test called an immunoassay, which mimics the action of the immune system to detect the presence of biomarkers – the chemicals associated with diseases. When biomarkers are present in samples, such as those taken from humans, the immunoassay test produces a fluorescent glow (light) that can be measured in a laboratory. The greater the glow, the more of the biomarker is present. However, if the amount of biomarker is too small, the fluorescent light is too faint to be detected, setting the limit of detection. A major goal in immunoassay research is to improve the detection limit.

The Princeton researchers tackled this limitation by using nanotechnology to greatly amplify the faint fluorescence from a sample. By fashioning glass and gold structures so small they could only be seen with a powerful electron microscope, the scientists were able to drastically increase the fluorescence signal compared to conventional immunoassays, leading to a 3-million-fold improvement in the limit of detection. That is, the enhanced immunoassay would require 3 million times fewer biomarkers to be present compared to a conventional immunoassay. (In technical terms, the researchers measured an improvement in the detection limit from 0.9 nanomolars to 300 attomolars.)

“This advance opens many new and exciting opportunities for immunoassays and other detectors, as well as in disease early detection and treatment,” said Stephen Chou, the Joseph C. Elgin Professor of Engineering, who led the research team. “Furthermore, the new assay is very easy to use, since for the person conducting the test, there will be no difference from the old one—they do the procedure in exactly the same way.” …

The research was published in Analytical Chemistry [abstract]. Such a large quantitative improvement in sensitivity could result in qualitative improvements in medical care, for example by enabling earlier detection of diseases like cancer and Alzheimer’s disease.
—James Lewis, PhD

Foresight Presents: “GENOGEN: Regenerating Skin for Life“
Dr. Nancy Mize
Date/Time: Thursday, May 31, 2012, 6:30pm in PDT
Drinks/Dinner: 6:30pm, Talk: 7:30pm
RSVP: $40 via http://www.paypal.com/ to foresight@foresight.org
Location: Ristorante Don Giovanni
235 Castro Street, Mountain View, CA 94041

GENOGEN is developing products that activate resident skin stem cells to stimulate local areas of regeneration of skin naturally – the way children heal. GENOGEN’s first product is a re-purposed agent, currently FDA and EU approved and marketed, and used in humans for over 5 years, with significant utility in the aesthetics sector for treatment of aging skin. Localized skin delivery of the stem cell activator with a growth matrix activates local regeneration and repair in situ – with no stem cell isolation, no stem cell prep, no surgery, extraction or re-implantation – resulting in accelerated healing and young skin.

NANCY K MIZE, PhD, Scientist, Innovator, and CEO of GENOGEN Inc., has researched stem cell activators since 2000, and is the co-inventor on 11 issued patents. Dr. Mize served as the BioMarker Expert for Personalized Medicine at Pacific BioDevelopment, the Director of Protein Bioinformatics at Hyseq/Nuvelo, and Scientist, Drug Delivery Technologies at Alza Corporation. Dr. Mize holds a PhD from UCSF in Cell Biology in the department of Human Physiology, BS from UC Berkeley and has completed Postdoctoral studies at the European Molecular Biology Laboratory (EMBL), Heidelberg, and Genentech.

Dmitri Lapotko. (Credit: Jeff Fitlow/Rice University)

In yet another wrinkle in the rapidly developing area of using nanotechnology to enhance cancer chemotherapy, targeted nanoparticles were used to produce “nanobubbles” inside cancer cells instead of to deliver a chemotherapy drug to the cancer cells. In laboratory tests, the nanobubbles proved to be much more efficient in specifically killing cancer cells while sparing neighboring healthy cells. A hat tip to ScienceDaily for reprinting this Rice University news release with its embedded video “‘Nanobubbles’ plus chemotherapy equals single-cell cancer targeting“:

Using light-harvesting nanoparticles to convert laser energy into “plasmonic nanobubbles,” researchers at Rice University, the University of Texas MD Anderson Cancer Center and Baylor College of Medicine (BCM) are developing new methods to inject drugs and genetic payloads directly into cancer cells. In tests on drug-resistant cancer cells, the researchers found that delivering chemotherapy drugs with nanobubbles was up to 30 times more deadly to cancer cells than traditional drug treatment and required less than one-tenth the clinical dose.

“We are delivering cancer drugs or other genetic cargo at the single-cell level,” said Rice’s Dmitri Lapotko, a biologist and physicist whose plasmonic nanobubble technique is the subject of four new peer-reviewed studies, including one due later this month in the journal Biomaterials and another published April 3 in the journal PLoS ONE [Open Access research article]. “By avoiding healthy cells and delivering the drugs directly inside cancer cells, we can simultaneously increase drug efficacy while lowering the dosage,” he said. …

Rice’s nanobubbles are not nanoparticles; rather, they are short-lived events. The nanobubbles are tiny pockets of air and water vapor that are created when laser light strikes a cluster of nanoparticles and is converted instantly into heat. The bubbles form just below the surface of cancer cells. As the bubbles expand and burst, they briefly open small holes in the surface of the cells and allow cancer drugs to rush inside. The same technique can be used to deliver gene therapies and other therapeutic payloads directly into cells.

This method, which has yet to be tested in animals, will require more research before it might be ready for human testing, said Lapotko, faculty fellow in biochemistry and cell biology and in physics and astronomy at Rice. …

To form the nanobubbles, the researchers must first get the gold nanoclusters inside the cancer cells. The scientists do this by tagging individual gold nanoparticles with an antibody that binds to the surface of the cancer cell. Cells ingest the gold nanoparticles and sequester them together in tiny pockets just below their surfaces.

While a few gold nanoparticles are taken up by healthy cells, the cancer cells take up far more, and the selectivity of the procedure owes to the fact that the minimum threshold of laser energy needed to form a nanobubble in a cancer cell is too low to form a nanobubble in a healthy cell

A given molecular targeting strategy can only achieve a certain ratio of entering cancer cells to entering healthy cells. As the cancer evolves to become more resistant to the drug, that ratio becomes inadequate to kill cancer cells while sparing healthy cells. But because the laser pulse can be precisely controlled, the ratio of gold nanoparticles in cancer cells to the amount in healthy cells is sufficient to ensure that nanobubbles only form in cancer cells, so the drug can only enter the cancer cells. If this approach works as well in an animal model as it does in laboratory cell cultures, it might develop into an effective therapy to kill drug-resistant tumor cells.
—James Lewis, PhD

One of the most promising current applications of nanotechnology to medicine is the use of nanoparticles to specifically target drug therapy to cancer cells. A variety of different types of nanoparticles using different drug delivery strategies are being investigated, including one type using biopolymers that we described here last week. Another report shows that a very different type of nanoparticle, composed of gold, works by delivering a drug directly to the nucleus of cancer cells. A hat tip to ScienceDaily for reprinting this news release from Northwestern University written by Megan Fellman “Tiny hitchhikers attack cancer cells: Gold nanostars first to deliver drug directly to cancer cell nucleus“:

Nanotechnology offers powerful new possibilities for targeted cancer therapies, but the design challenges are many. Northwestern University scientists now are the first to develop a simple but specialized nanoparticle that can deliver a drug directly to a cancer cell’s nucleus — an important feature for effective treatment.

They also are the first to directly image at nanoscale dimensions how nanoparticles interact with a cancer cell’s nucleus.

“Our drug-loaded gold nanostars are tiny hitchhikers,” said Teri W. Odom, who led the study of human cervical and ovarian cancer cells. “They are attracted to a protein on the cancer cell’s surface that conveniently shuttles the nanostars to the cell’s nucleus. Then, on the nucleus’ doorstep, the nanostars release the drug, which continues into the nucleus to do its work.” …

Using electron microscopy, Odom and her team found their drug-loaded nanoparticles dramatically change the shape of the cancer cell nucleus. What begins as a nice, smooth ellipsoid becomes an uneven shape with deep folds. They also discovered that this change in shape after drug release was connected to cells dying and the cell population becoming less viable — both positive outcomes when dealing with cancer cells.

The results are published in the journal ACS Nano [abstract].

Since this initial research, the researchers have gone on to study effects of the drug-loaded gold nanostars on 12 other human cancer cell lines. The effect was much the same. “All cancer cells seem to respond similarly,” Odom said. “This suggests that the shuttling capabilities of the nucleolin protein for functionalized nanoparticles could be a general strategy for nuclear-targeted drug delivery.”

The nanoparticle is simple and cleverly designed. It is made of gold and shaped much like a star, with five to 10 points. (A nanostar is approximately 25 nanometers wide.) The large surface area allows the researchers to load a high concentration of drug molecules onto the nanostar. Less drug would be needed than current therapeutic approaches using free molecules because the drug is stabilized on the surface of the nanoparticle.

The drug used in the study is a single-stranded DNA aptamer called AS1411. Approximately 1,000 of these strands are attached to each nanostar’s surface.

The DNA aptamer serves two functions: it is attracted to and binds to nucleolin, a protein overexpressed in cancer cells and found on the cell surface (as well as within the cell). And when released from the nanostar, the DNA aptamer also acts as the drug itself.

Bound to the nucleolin, the drug-loaded gold nanostars take advantage of the protein’s role as a shuttle within the cell and hitchhike their way to the cell nucleus. The researchers then direct ultrafast pulses of light — similar to that used in LASIK surgery — at the cells. The pulsed light cleaves the bond attachments between the gold surface and the thiolated DNA aptamers, which then can enter the nucleus.

In addition to allowing a large amount of drug to be loaded, the nanostar’s shape also helps concentrate the light at the points, facilitating drug release in those areas. Drug release from nanoparticles is a difficult problem, Odom said, but with the gold nanostars the release occurs easily.

That the gold nanostar can deliver the drug without needing to pass through the nuclear membrane means the nanoparticle is not required to be a certain size, offering design flexibility. Also, the nanostars are made using a biocompatible synthesis, which is unusual for nanoparticles.

Odom envisions the drug-delivery method, once optimized, could be particularly useful in cases where tumors are fairly close to the skin’s surface, such as skin and some breast cancers. (The light source would be external to the body.) Surgeons removing cancerous tumors also might find the gold nanostars useful for eradicating any stray cancer cells in surrounding tissue.

A particular advantage of these nanostars is that the plasmonic electrons produced on the surface of the nanostars by the laser solves the problem of how to efficiently discharge the drug target from the nanoparticle vehicle.
—James Lewis, PhD

An artist's rendering of BIND-014. Image credit: Digizyme, Inc.

We have often reported here that targeted nanoparticles to treat cancer have shown great promise in animal studies. An MIT news release written by Anne Trafton now informs us that “Targeted nanoparticles show success in clinical trials“:

Targeted therapeutic nanoparticles that accumulate in tumors while bypassing healthy cells have shown promising results in an ongoing clinical trial, according to a new paper.

The nanoparticles feature a homing molecule that allows them to specifically attack cancer cells, and are the first such targeted particles to enter human clinical studies. Originally developed by researchers at MIT and Brigham and Women’s Hospital in Boston, the particles are designed to carry the chemotherapy drug docetaxel, used to treat lung, prostate and breast cancers, among others.

In the study, which appears April 4 in the journal Science Translational Medicine [abstract], the researchers demonstrate the particles’ ability to target a receptor found on cancer cells and accumulate at tumor sites. The particles were also shown to be safe and effective: Many of the patients’ tumors shrank as a result of the treatment, even when they received lower doses than those usually administered.

“The initial clinical results of tumor regression even at low doses of the drug validates our preclinical findings that actively targeted nanoparticles preferentially accumulate in tumors,” says Robert Langer, the David H. Koch Institute Professor in MIT’s Department of Chemical Engineering and a senior author of the paper. “Previous attempts to develop targeted nanoparticles have not successfully translated into human clinical studies because of the inherent difficulty of designing and scaling up a particle capable of targeting tumors, evading the immune system and releasing drugs in a controlled way.”

The Phase I clinical trial was performed by researchers at BIND Biosciences, a company cofounded by Langer and Omid Farokhzad in 2007.

“This study demonstrates for the first time that it is possible to generate medicines with both targeted and programmable properties that can concentrate the therapeutic effect directly at the site of disease, potentially revolutionizing how complex diseases such as cancer are treated,” says Farokhzad, director of the Laboratory of Nanomedicine and Biomaterials at Brigham and Women’s Hospital, associate professor of anesthesia at Harvard Medical School and a senior author of the paper. …

The news release goes on to detail several features of these nanoparticles that may be useful in evaluating other types of nanoparticles that are currently at earlier stages of development and have only been tested in animal models. First of all, nanoparticles of many different compositions have been developed, from gold to DNA. These, called AccurinsTM, use clinically validated biocompatible polymers and incorporate a “stealth” layer to avoid removal by the immune system. As explained in the news release:

One of the challenges in developing effective drug-delivery nanoparticles, Langer says, is designing them so they can perform two critical functions: evading the body’s normal immune response and reaching their intended targets.

“You need exactly the right combination of these properties, because if they don’t have the right concentration of targeting molecules, they won’t get to the cells you want, and if they don’t have the right stealth properties, they’ll get taken up by macrophages,” says Langer, also a member of the David H. Koch Institute for Integrative Cancer Research at MIT.

The BIND-014 nanoparticles have three components: one that carries the drug, one that targets PSMA, and one that helps evade macrophages and other immune-system cells. A few years ago, Langer and Farokhzad developed a way to manipulate these properties very precisely, creating large collections of diverse particles that could then be tested for the ideal composition.

“They systematically made a set of materials that varied in the properties they thought would matter, and developed a way to screen them. That’s not been done in this kind of setting before,” says Mark Saltzman, a professor of biomedical engineering at Yale University who was not involved in this study. “They’ve taken the concept from the lab into clinical trials, which is quite impressive.”

The systematic way in which these researchers addressed multiple variables and issues gives us some indication of what will be required to move nanoparticles and other nanotherapeutics from laboratory studies into clinical trials.
—James Lewis, PhD

Credit: Image courtesy of University of Texas at Austin

“Hindlimb ischemia was created in rats and treatments were delivered over seven days with an osmotic pump. The laser doppler imaging above shows the rat’s hind limb prior to treatment (on the left) and with increased blood flow (image on the right) just seven days after treatment.”

A major advantage of nanoparticles used in nanomedicine is that they can combine and deliver together more than one therapeutic component. This capability has been brought to bear in the quest to encourage regenerative blood vessel growth after ischemic disease, which causes much cardiovascular morbidity. Delivering a growth factor in a nanoparticle containing a different biomolecule as a coreceptor achieves results where delivering the factor alone had failed. A hat tip to ScienceDaily for reprinting this University of Texas at Austin news release “New Ability to Regrow Blood Vessels Holds Promise for Treatment of Heart Disease“:

University of Texas at Austin researchers have demonstrated a new and more effective method for regrowing blood vessels in the heart and limbs — a research advancement that could have major implications for how we treat heart disease, the leading cause of death in the Western world.

The treatment method developed by Cockrell School of Engineering Assistant Professor Aaron Baker could allow doctors to bypass surgery and instead repair damaged blood vessels simply by injecting a lipid-incased substance into a patient. Once inside the body, the substance stimulates cell growth and spurs the growth of new blood vessels from pre-existing ones.

The method has been tested successfully on rats, and findings of the study were published recently in the Proceedings of the National Academy of Sciences [abstract].

“Others have tried using growth factors to stimulate vessel growth in clinical trials and have not been successful,” said Baker, a faculty member in the school’s Department of Biomedical Engineering. “We think that a major reason for this is that previous methods assumed that the diseased tissues retained the ability to respond to a growth stimulus. Our method basically delivers extra components that can restore growth factor responsiveness to the tissue of patients with long-standing clinical disease.”

The ability to regrow blood vessels could prove crucial to treating chronic myocardial ischemia disease, which affects up to 27 million patients in the U.S. and leads to a reduction of blood flow in the heart and lower limbs — ultimately causing organ dysfunction and failure. …

The new method introduced by Baker and his research team builds on a promising revascularization approach that, up until now, has shown limited efficacy in clinical trials for treating human disease.

The method combines a growth factor — a substance capable of stimulating cellular growth, proliferation and cellular differentiation, as well as healing wounds — known as fibroblast growth factor 2 (FGF-2) with a lipid-embedded receptor to enhance its activity.

A challenge for scientists and engineers, however, has been getting FGF-2 to bind with cell receptors — the very molecules often found on the surface of the cell that receive chemical signals and direct activity in the cell from outside sources.

To overcome this, Baker’s method embeds the growth factors in synthetic lipid-based nanoparticles containing a coreceptor known as syndecan-4. The nanoparticles containing co-receptors that, when delivered with the growth factor, enable improved cell binding so that the growth factor can direct the targeted cell to divide, proliferate and form new cells for tissue regrowth.

The incased substance was injected into rats with hindlimb ischemia and stimulated a complete recovery from the ischemia in just seven days.

Mammalian cells are very complex mechanisms, and several decades of experience with biotechnology have demonstrated that newly discovered molecules expected to do great things often underperform expectations because changing a cell requires several molecules working together. Nanoparticles have the potential to be complex enough to accomplish what single molecules cannot.
—James Lewis, PhD