Safer Light-Activated Nanoparticle Cancer Therapy

Oncologists have long suspected that photodynamic therapy could find broader use if only there was some way to limit the accumulation of photosensitizer molecules to tumors, sparing healthy tissue from unintended damage. Now, using modified silica nanoparticles, a team of investigators at the State University of New York, Buffalo, has developed a photosensitizer delivery method that has the potential to target tumor cells specifically.

His group has used porous silica nanoparticles modified in such a way as to form a strong chemical bond between the nanoparticles and the photosensitizer molecules. When exposed to light, the permanently entrapped photosensitizer still produces reactive oxygen molecules that can diffuse out of the nanoparticles through their porous silica shells.

The investigators found, too, that human colon cancer cells readily take up the photosensitizer-loaded nanoparticles. More importantly, shining light on these cells resulted in their death.

Coated carbon nanotubes retain ability to bind to drugs and imaging agents

In the quest to turn carbon nanotubes from nanoscale wonder into clinically useful drug and imaging agent delivery agents, researchers have often added polymer coatings to the outside of the nanotubes in order to render them biocompatible. Now, researchers at Stanford University have found that even when coated, carbon nanotubes retain the ability to bind extraordinarily large numbers of drug and imaging agent molecules in a stable yet reversible manner.

Reporting its work in the journal ACS Nano, a research team led by Hongjie Dai, Ph.D., an investigator in the Center for Cancer Nanotechnology Excellence Focused on Therapy Response, showed that polymer-coated single-walled carbon nanotubes spontaneously absorbed the cancer drug doxorubicin onto their surfaces when the drug was added to the nanotubes dissolved in water. The resulting construct contained approximately 50 to 60 percent doxorubicin by weight, far higher than the 8 to 10 percent obtained with either liposomes or dendrimers.

More SENS3 Reports

Matthew S. O’Connor (okee, a.k.a. Dr. Okie) reports on the SENS3 conference on life extension at the Ouroboros website. Okee is currently a postdoctoral fellow at UC Berkeley, Bioengineering Department in the laboratory of Dr. Irina Conboy.

Biomedical remediation (essentially the brain-child of Aubrey de Grey) is moving along quickly.

Two teams have identified strains of bacteria capable of using 7-ketocholesterol (one precursor of the poorly defined lipofuscin) as energy. The next goal is to clone the genes. After that they want to purify the enzyme responsible and feed it to people and see if it will break down our lipofuscin.

Okee's issue:

is that they are trying to solve a problem that hasn’t been proved to be a problem yet. Lipofuscin accumulation has long been associated with aging in many tissues, but never (as far as I am aware) proved to be responsible for any illness, ailment, or disease. Now, don’t get me wrong, Aubrey makes an excellent argument for this being a serious problem with no traditional biomedical solution in sight, but it’s still just theory.

In Okee's opinion:
wound healing and artificial repair was the most provocative and promising aspect of the research at SENS 3.

Cato Laurencin has an approach called “regenerative engineering.”

Okee's comment:

It was amazing, however, to see someone actually using a few in something practical! In my opinion, this is the reality of regenerative medicine: an innovative surgeon combining technology and knowledge of biology to partially repair injuries such that they will heal as well, or better than they started.

Dr. Laurencin showed results from his work on 3D absorbable poly L-lactide (PLLA) scaffolds that seem to promote recovery from surgery much more efficiently than traditional methods. This is a microsphere-based scaffold, which promotes efficient invasion and engraftment of osteoblasts to help repair bone. He is also investigating surfaces with nano-scale grooves, which are more conducive to mesenchymal stem cell proliferation.

There is scarless repair of brain tissue using nanofibers to accelerate the healing:

Rutledge Ellis-Behnke spoke on his work with SAPNS: Self Assembling Peptide Nanofiber Scaffold. Essentially, he squirts a solution containing these nanofibers into wound sites and reportedly achieves amazing results. He reports dramatic recovery from serious brain injury: both scarless repair of bulk brain tissue removal and reinnervation. In addition, he claims that the nanofibers can dramatically stop bleeding in wounds (he showed video of this). These results are so dramatic that they are almost unbelievable.

From the research paper [they are stopping bleeding in the brain in 15 seconds]:

This novel therapy stops bleeding without the use of pressure, cauterization, vasoconstriction, coagulation, or cross-linked adhesives. The self-assembling solution is nontoxic and nonimmunogenic, and the breakdown products are amino acids, which are tissue building blocks that can be used to repair the site of injury. Here we report the first use of nanotechnology to achieve complete hemostasis in less than 15 seconds, which could fundamentally change how much blood is needed during surgery of the future.

Two groups and three speakers addressed the issue of aged muscle, muscle regeneration, and muscle stem cells.

One of the groups work supports the idea that muscle stem cells remain intrinsically young, even while their tissue ages around them. Another group revitalized old muscle stem cells.

A startup company, Sangamo, has developed gene editing, which different from gene therapy. It’s not introducing exogenous DNA into your cells, it’s editing your genomic DNA.

One drawback for Dr Cui GIFT method of cancer treatment is that it requires 10 donors for every recipient. I speculate, we will probably need to use telomeres and culturing of cells to increase the volume of cells for donation.

Quick and dirty advice for keeping nanotech clean

IEEE Spectrum discusses how to keep nanoparticles safe

There is a growing body of evidence that ­nanotechnological chemicals and related substances could pollute the air, soil, and water and damage human health. Preliminary studies from Arizona State University suggest that nanoparticles accumulate in the food chain and could cause problems later on. There is an opportunity to deploy nanoparticles properly.

We need to look at nano­technology broadly, anticipate its adverse effects, and prevent problems. Prudently avoiding a crisis is always better than trying to repair damage later on.

The IEEE Spectrum article is discussing nanotechnology to mean:

When we talk about nanotechnology, we mean that the materials involved exist as microscopic particles with at least one dimension that is between 1 and 100 nanometers. To put this in perspective, consider that the typi­cal nanosize particle of titanium dioxide in sunscreen is 20 nm in diameter. The particle is a clump of about a ­million molecules. A grain of pollen is about 1000 times the size of this titanium dioxide nano­particle; bacterial cells are around 100 times as large, and the width of a human hair is about 4000 times as great.

Nanotechnology refers to manufactured materials in the nanosize range, or to manufactured products containing these materials.

The health risks and concerns of nanoparticles:
In 2003, Chiu-wing Lam of NASA’s Johnson Space Center, in Houston, instilled carbon

nanotubes into the lungs of mice and reported that they triggered granulomas, or areas of ­inflammation. In a similar experiment, David Warheit at Dupont’s Haskell Laboratory for Toxicity and Industrial Medicine, in Newark, Del., found such inflammation in rats’ lungs in the same year. Perhaps most troubling of all, nanoparticles can make their way into the brain by passing from the nose through the blood-brain barrier, a membrane that protects the brain from chemicals in the blood while allowing oxygen, carbon dioxide, sugars, and certain amino acids to pass through unaltered.

In 2004, experiments by Eva Oberdörster, a lecturer in bio­logical sciences at Southern Methodist University, in Dallas, found that the buckyball, a nanostructure made of carbon atoms, can penetrate the brains of bass via the gills. There, the nanoparticles trigger a reaction in brain enzymes called oxidative stress, a change in brain chemistry that indicates harm. Eva Oberdörster (a daughter of Günter) also discovered that buckyballs are toxic to daphnia, tiny freshwater fleas used to test toxicity in aquatic systems [see photo, “Aquatic Mine Canaries”]. The buckyballs did not clump together and sink harmlessly to the bottom of the test sites as researchers had expected.

Researchers are also concerned about persistence. Because of their small size and light weight, nanoparticles can stay aloft in the upper atmosphere much longer than coarse particulate air pollutants, and current filter technologies for controlling particles have holes that are a thousand times too big to trap nanoparticles. Nanoparticles may also bioaccumulate. For example, bacteria can ingest them, so the particles could become part of our food chain. And we know that chemical pollutants, like some pesticides, can also accumulate in the chain. At the moment, though, we don’t know what effect nanomaterials will have on the food supply.

Good things that are happening and green nanotechnology trends to continue:

One bright sign is that industry groups and government agencies are beginning to include concerns about nanotechnology in their long-term research planning. An encouraging new initiative is Green Nanotechnology, pioneered by the EPA and the Woodrow Wilson Inter­national Center for Scholars, in Washington, D.C. The two organizations are developing a framework and recommended practices that would help prevent manufacturers from releasing substances currently recognized as pollutants into the atmosphere, as well as prevent the manufacture of products containing nanomaterials that would knowingly harm the environment. The development of guidelines for Green Nanotechnology would let consumers or governments reward companies that are performing well, on the model of Energy Star, a joint program of the EPA and the Department of Energy. It sets guidelines for energy efficiency of consumer products and allows products that meet those guidelines to display Energy Star labels.

Recently, there was a small but significant victory: manufacturers of gold nanoparticles used for paint and, potentially, environmental cleanup and cancer treatment, developed a manufacturing method that eliminated the use of a toxic organic chemical and replaced it with water, reducing energy use at the same time.

Green Nano also means using nanotechnology itself to clean up production processes. The semiconductor industry can replace dangerous chemicals such as the perfluorooctane sulfonate polymers used in photo resists, antireflective coatings, and reagents with less toxic nano alternatives. Nanomembranes can filter out waste and pollutants in chemical processes. Nano-enabled sensors can improve process control and monitor emissions. Nanoproducts that improve energy efficiency, such as solar cells or better conducting materials, indirectly improve the environment through lower power-plant emissions.

Researchers set new record for brightness of quantum dots

By placing quantum dots on a specially designed photonic crystal, researchers at the University of Illinois have demonstrated enhanced fluorescence intensity by a factor of up to 108. Potential applications include high-brightness light-emitting diodes, optical switches and personalized, high-sensitivity biosensors.

A quantum dot is a tiny piece of semiconductor material 2 to 10 nanometers in diameter (a nanometer is 1 billionth of a meter). When illuminated with invisible ultraviolet light, a quantum dot will fluoresce with visible light.

To enhance the fluorescence, Cunningham and colleagues at the U. of I. begin by creating plastic sheets of photonic crystal using a technique called replica molding. Then they fasten commercially available quantum dots to the surface of the plastic.

Quantum dots normally give off light in all directions. However, because the researchers’ quantum dots are sitting on a photonic crystal, the energy can be channeled in a preferred direction – toward a detector, for example.

While the researchers report an enhancement of fluorescence intensity by a factor of up to 108 compared with quantum dots on an unpatterned surface, more recent (unpublished) work has exceeded a factor of 550.

“The enhanced brightness makes it feasible to use photonic crystals and quantum dots in biosensing applications from detecting DNA and other biomolecules, to detecting cancer cells, spores and viruses,” Cunningham said. “More exotic applications, such as personalized medicine based on an individual’s genetic profile, may also be possible.”

Nanoparticle Vaccine Is Both More Effective And Less Expensive

from Sciencedaily, bioengineering researchers from the EPFL in Lausanne, Switzerland, have developed and patented a nanoparticle that can deliver vaccines more effectively, with fewer side effects, and at a fraction of the cost of current vaccine technologies.

This technology may make it possible to vaccinate against diseases like hepatitis and malaria with a single injection. And at an estimated cost of only a dollar a dose, this technology represents a real breakthrough for vaccine efforts in the developing world.

Thanks to recent advances, an immune response can be triggered with just a single protein from a virus or bacterium. Recent research has also shown that the best way to get sustained immunity is to deliver an antigen directly to specialized immune cells known as dendritic cells (DCs). Current methods have trouble obtaining an adequate immune response with a single injection and can cause side effects or even be toxic.

EPFL professors Jeff Hubbell and Melody Swartz and PhD student Sai Reddy have engineered nanoparticles that completely overcome these limitations. At a mere 25 nanometers, these particles are so tiny that once injected, they flow through the skin's extracellular matrix, making a beeline to the lymph nodes. Within minutes, they've reached a concentration of DCs thousands of times greater than in the skin. The immune response can then be extremely strong and effective.

In addition, the EPFL team has also engineered a special chemical coating for the nanoparticles that mimics the surface chemistry of a bacterial cell wall. The DCs don't recognize this as a specific invader, but do know that it's something foreign, and so a low-level, generic immune reaction known as "complement" is triggered. This results in a particularly potent immune response without the risk of unpleasant or toxic side effects.

Cost and logistics are important factors, especially for use in developing countries. Unlike other nanoparticle vaccine technologies that degrade in water and thus require expensive drying and handling procedures, the EPFL team's nanoparticles won't degrade until they are in the body. They are in liquid form and don't require refrigeration, so preparation and handling costs are reduced, and they are easy to transport.

More study is required to achieve these goals," she adds, "but we have every reason to believe this technique could be in use within five years."

Roche-Ventana would further gene diagnostics and treatment

Businessweek reports on a possible merger of Roche-Ventana

Swiss Pharmaceutical giant Roche Holdings (RMMBY ) caught Wall Street by surprise in June when it launched a $75-a-share hostile bid for Ventana Medical Systems (VMSI ). The Tucson company pulled in just $238 million last year selling tools that help doctors analyze tissue samples to diagnose cancer. Roche's bid values the company at about $3 billion.

What Roche and Ventana share is an intimate understanding of the next revolution in medicine. In the coming decade, pharmaceutical products--especially cancer drugs--will be created in tandem with diagnostic tests that tell doctors which patients are likely to benefit. Right now, physicians often feel they're flying blind. Each patient arrives at the hospital with a unique genetic makeup, which affects whether a prescribed drug will kill tumor cells, cause devastating side effects, or possibly do nothing at all. If a new generation of gene tests can help predict these different outcomes, patients will be spared expensive and unhelpful ordeals. The pool of target patients for many medications will also shrink. But if doctors are confident a drug will help somebody, they'll prescribe it aggressively, and insurers will be more likely to foot the bill.

Roche is the most ardent evangelist for this pairing of drugs with gene-based diagnostics--an approach called personalized medicine.

Ventana and Roche both are facing regulatory hurdles. At present, the Food & Drug Administration has separate channels for reviewing drugs and diagnostics, and no procedure for reviewing them in combination.

For experts like Abrahams, the logic in pairing tests and treatments is irrefutable.

Introduction to nanopharmaceuticals

Nanomedicine is the medical application of nanotechnology. It covers areas such as nanoparticle drug delivery and possible future applications of molecular nanotechnology (MNT) and nanovaccinology.

A definition from the Academy of Pharmaceutical Sciences of Great Britain.

Nanopharmaceuticals represent an emerging field where the nanoscale element may refer to either the size of the drug particle or to a therapeutic delivery system. These therapeutic systems may be defined as a complex system consisting of at least two components, one of which is the active ingredient. In this field the concept of nanoscale is the range from 1 to 1,000nm. The definition includes polymer therapeutics, which share many characteristics with macromolecular prodrugs such as antibody conjugates of drugs.

The European Science Foundation definition.

Nanopharmaceuticals can be developed either as drug delivery systems or biologically active drug products.

This sub-discipline is defined as the science and technology of nanometre size scale complex systems, consisting of at least two components, one of which being the active ingredient. In this field the concept of nanoscale was seen to range from 1 to 1000 nm.

Nanopharmaceuticals as a big part of what nanomedicine is today. From the Ruth Duncan presentation.

Various kinds of nanoscale particles used for nanopharmaceuticals

Nanoparticles is a microscopic particle with at least one dimension less than 100 nm.

Liposomes is a spherical vesicle composed of a bilayer membrane. In biology, this specifically refers to a membrane composed of a phospholipid and cholesterol bilayer

Antibody conjugates
A conjugate vaccine is created by covalently attaching a poor antigen to a carrier protein, thereby conferring the immunological attributes of the carrier on the attached antigen. This technique for the creation of an effective immunogen is most often applied to bacterial polysaccharides for the prevention of invasive bacterial disease.

polymer therapeutics

From the Ruth Duncan presentation

Buckyballs and Nanotubes

Nanoemulsions is a type of emulsion in which the sizes of the particles in the dispersed phase are defined as less than 1000 nanometers. A nanoemulsion of soybean oil to create drops of 400-600 nanometers in diameter will kill many pathogens such as bacteria and viruses.

Quantum Dots is a semiconductor nanostructure that confines the motion of conduction band electrons, valence band holes, or excitons (bound pairs of conduction band electrons and valence band holes) in all three spatial directions. The confinement can be due to electrostatic potentials (generated by external electrodes, doping, strain, impurities), the presence of an interface between different semiconductor materials (e.g. in core-shell nanocrystal systems), the presence of the semiconductor surface (e.g. semiconductor nanocrystal), or a combination of these

Small quantum dots, such as colloidal semiconductor nanocrystals, can be as small as 2 to 10 nanometers, corresponding to 10 to 50 atoms in diameter and a total of 100 to 100,000 atoms within the quantum dot volume. Self-assembled quantum dots are typically between 10 and 50 nm in size. Quantum dots defined by lithographically patterned gate electrodes, or by etching on two-dimensional electron gases in semiconductor heterostructures can have lateral dimensions exceeding 100 nm. At 10 nm in diameter, nearly 3 million quantum dots could be lined up end to end and fit within the width of a human thumb.

Dendrimers - Dendrimers are synthetic polymers, a thousand times smaller than cells. Dendrimers can be synthesized in various predetermined sizes, and can interact with biological agents by modifying their surface properties.

FURTHER READING
An article on nanopharmaceuticals and veterinary medicine

Presentation by Ruth Duncan on nanopharmaceuticals

A nanopharmaceuticals site

Launching nanoparticle drug delivery site

Here is the start of my site devoted to nanoparticle drug delivery. I am providing it as a service so that fewer people will need to buy overpriced market reports on the same subject. I will also launch several other sites on near term nanotechnology subjects. My main website on future technology with a significant focus on advanced nanotechnology is advancednano

The Drug delivery is a multi-billion dollar business. Some calculate it as a 9.8 billion business. Led by the strong growth of biotechnology drugs requiring novel delivery technologies, the injectable/implantable drug delivery market reached revenues of $9.8 billion in 2006

Nanotechnology in drug delivery

A drug delivery website

Drug delivery stocks

The 9th annual drug delivery symposium coming Dec 16-20, 2007 is only about $600 versus $5000 or more for some market reports

Advance Nanotech Singapore Pte. Ltd. owns 75% of Nano Solutions Limited (Imperial College, London) which is developing Nanovindex. Nanovindex is a nanoparticle-hydrogel composites for drug delivery.

From 2005, 10Q

Nanotechnologies have already begun to change the scale and methods of drug delivery and hold huge potential for future developments in this area. Nanotechnology can provide new formulations and routes for drug delivery that broaden their therapeutic potential enormously by allowing the delivery of new types of medicine to previously inaccessible sites in the body. Novel composites incorporating nanoparticles are particularly exciting for these applications. A key to gaining competitiveness within the market is to develop next generation composites which are extremely sensitive to a variety of environmental stimuli. NanoVindex aims to achieve this by utilising expertise in rational peptide design to incorporate specific pH, enzymes and temperature triggers within the composites enabling a new level of control over the release of encapsulated drugs.

Technology

NanoVindex is seeking to develop a platform technology of nanoparticle-hydrogel composites for tailored drug delivery applications. The development shall leverage the research of Imperial College London in rational design of self-assembling peptide systems, control over the nanoscale organic/inorganic interface, and physiologically responsive bio-nano materials. Revenues to drug delivery companies were $1.3bn in 2002 and projected to increase to $6.7bn by 2012. With the focus evermore on emerging nanotechnologies and the improvements these may offer over more conventional systems, the market for new nanotechnologies in drug delivery is poised to be a multi-billion dollar arena. These technologies have the potential to revolutionise the pharmaceutical industry.

FURTHER READING
Abstract on Hydrogel-Nanofiber Composite Systems For Drug Delivery

2003 patent, Composite hydrogel drug delivery systems

google search of hydrgel composites drug delivery

Google search on nanoparticle drug delivery

Other drug delivery market studies by Kalorama