Nanoparticle enabled cooking of cancer tumors moving to clinical trials in about three year

Kanzius RF therapy attaches microscopic nanoparticles to cancer cells and then "cooks" tumors inside the body with harmless radio waves could be in clinical trials as early as 3 years. The treatment has been 100% effective in animal trials.

Novozymes and Upperton Collaborate on New Nanoparticle Drug Delivery

Nanowerk reports that Novozymes announced a new collaboration agreement with Upperton Limited, a UK based Biotech Company specialising in novel nanoparticle-based drug delivery systems.

The two companies and will focus on the commercial exploitation of the jointly-owned rP-nano™ technology: a highly targeted drug delivery system which utilises the natural binding properties of recombinant protein nanoparticles to enhance drug and gene bioavailability.

They generate nanoparticles from recombinant proteins in a yeast-based expression system. rP-nano™ technology can generate precisely-sized nanoparticles within the range of 10nm to 120nm and can be optimised for Enhanced Permeability and Retention effect. The nanoparticles produced through this process retain the natural binding properties of the recombinant proteins from which they are made, and bind to specific cell types to enable more targeted drug delivery and improved bioavailability.

Silica nanoparticles more effectively deliver bacteria killing nitric oxide

Mark Schoenfisch and his lab of analytical chemists at UNC have created nano-scale scaffolds made of silica and loaded with nitric oxide (NO) which can be released in a precisely controlled way. Nitric Oxide can be used to kill bacteria.

Schoenfisch, Hetrick and their colleagues tested their silica scaffolds head-to-head with small molecules against the bacteria Pseudomonas aeruginosa, which is commonly found in burn and other wound infections.

NO delivered by both methods completely killed the bacteria. But the silica nanoparticles delivered the NO right to the bacteria’s doorstep. In contrast, the small molecules released NO indiscriminately, and the concentration of NO is lost as it makes its way toward bacterial cells.

“With the silica particles, more NO actually reached the inside of the cells, enhancing the efficacy of the nanoparticles compared to the small molecule. So, the overall amount of NO needed to kill bacteria is much less with silica nanoparticles,” Schoenfisch said. “And, with small molecules, you’re left with potentially toxic byproducts,” Schoenfisch said. Using mouse cells, they proved that the silica nanoparticles weren’t toxic to healthy cells, but the small molecules were.

Future research will include studying additional bacterial strains, active targeting, preferential uptake and biodistribution studies.

Magnetic Nanoparticles could be used to control uptake of drugs by cell receptors

For the first time, researchers have demonstrated a means of controlling cell functions with a physical, rather than chemical, signal. Immune cells coated with nanoparticles take up calcium in the presence of a magnetic field. Each nanoparticle measures approximately 30 nanometers in diameter.

In this image, yellow cells are taking up calcium in response to a localized magnetic field. Cells that are farther away from the field are shown in purple and do not take up calcium. Credit: Donald Ingber, Harvard Medical School

Using a magnetic field to pull together tiny beads targeted to particular cell receptors, Harvard researchers made cells take up calcium, and then stop, then take it up again.

This is another important step to cellular and molecular control to enable nanomedicine

Ingber's group demonstrated its method for biomagnetic control using a type of immune-system cell that mediates allergic reactions.

Targeted nanoparticles with iron oxide cores were used to mimic antigens in vitro. Each is attached to a molecule that in turn can attach to a single receptor on an immune cell. When Ingber exposes cells bound with these particles to a weak magnetic field, the nanoparticles become magnetic and draw together, pulling the attached cell receptors into clusters. This causes the cells to take in calcium. (In the body, this would initiate a chain of events that leads the cells to release histamine.) When the magnetic field is turned off, the particles are no longer attracted to each other, the receptors move apart, and the influx of calcium stops.

"It's not the chemistry; it's the proximity" that activates such receptors, says Ingber.

The approach could have a far-reaching impact, as many important cell receptors are activated in a similar way and might be controlled using Ingber's method.

"In recent years, there has been a realization that physical events, not just chemical events, are important" to cell function, says Shu Chien, a bioengineer at the University of California, San Diego. Researchers have probed the effects of physical forces on cells by, for example, squishing them between plates or pulling probes across their surfaces. But none of these techniques work at as fine a level of control as Ingber's magnetic beads, which act on single biomolecules.

Many drugs, from anticancer antibodies to hormones, work by activating cell receptors. Once a hormone is in the blood, however, there's no turning it on or off. "This shows that you can turn on and off the signal, and that you can do it instantly," says Christopher Chen, a bioengineer at the University of Pennsylvania. "That's something that's hard to do, for example, with an antibody."

Ingber has many ideas for devices that might integrate his method of cellular control. Magnetic pacemakers could use cells instead of electrodes to send electrical pulses to the heart. Implantable drug factories might contain many groups of cells, each of which makes a different drug when activated by a magnetic signal. Biomagnetic control might lead to computers that can take advantage of cells' processing power. "Cells do complex things like image processing so much better than computers," says Ingber. Ingber, who began the project in response to a call by the Defense Advanced Research Projects Agency for new cell-machine interfaces, acknowledges that his work is in its early stages. In fifty years, however, he expects that there will be devices that "seamlessly interface between living cells and machines."

FURTHER READING
Harvard Institute for Biologically Inspired Engineering.

Nanodiamonds delivery chemotherapy drugs without negative side effects

Northwestern University researchers have shown that nanodiamonds -- much like the carbon structure as that of a sparkling 14 karat diamond but on a much smaller scale -- are very effective at delivering chemotherapy drugs to cells without the negative effects associated with current drug delivery agents.

Their study, published online by the journal Nano Letters, is the first to demonstrate the use of nanodiamonds, a new class of nanomaterials, in biomedicine. In addition to delivering cancer drugs, the model could be used for other applications, such as fighting tuberculosis or viral infections, say the researchers.

Nanodiamonds promise to play a significant role in improving cancer treatment by limiting uncontrolled exposure of toxic drugs to the body. The research team reports that aggregated clusters of nanodiamonds were shown to be ideal for carrying a chemotherapy drug and shielding it from normal cells so as not to kill them, releasing the drug slowly only after it reached its cellular target.

To make the material effective, Ho and his colleagues manipulated single nanodiamonds, each only two nanometers in diameter, to form aggregated clusters of nanodiamonds, ranging from 50 to 100 nanometers in diameter. The drug, loaded onto the surface of the individual diamonds, is not active when the nanodiamonds are aggregated; it only becomes active when the cluster reaches its target, breaks apart and slowly releases the drug. (With a diameter of two to eight nanometers, hundreds of thousands of diamonds could fit onto the head of a pin.)

“The nanodiamond cluster provides a powerful release in a localized place -- an effective but less toxic delivery method,” said co-author Eric Pierstorff, a molecular biologist and post-doctoral fellow in Ho’s research group. Because of the large amount of available surface area, the clusters can carry a large amount of drug, nearly five times the amount of drug carried by conventional materials.

Liposomes and polymersomes, both spherical nanoparticles, currently are used for drug delivery. While effective, they are essentially hollow spheres loaded with an active drug ready to kill any cells, even healthy cells that are encountered as they travel to their target. Liposomes and polymersomes also are very large, about 100 times the size of nanodiamonds -- SUVs compared to the nimble nanodiamond clusters that can circulate throughout the body and penetrate cell membranes more easily.

Unlike many of the emerging nanoparticles, nanodiamonds are soluble in water, making them clinically important. “Five years ago while working in Japan, I first encountered nanodiamonds and saw it was a very soluble material,” said materials scientist Houjin Huang, lead author of the paper and also a post-doctoral fellow in Ho’s group. “I thought nanodiamonds might be useful in electronics, but I didn’t find any applications. Then I moved to Northwestern to join Dean and his team because they are capable of engineering a broad range of devices and materials that interface well with biological tissue. Here I’ve focused on using nanodiamonds for biomedical applications, where we’ve found success.

“Nanodiamonds are very special,” said Huang. “They are extremely stable, and you can do a lot of chemistry on the surface, to further functionalize them for targeting purposes. In addition to functionality, they also offer safety -- the first priority to consider for clinical purposes. It’s very rare to have a nanomaterial that offers both.”

“It’s about optimizing the advantages of a material,” said Ho, a member of the Lurie Cancer Center. “Our team was the first to forge this area -- applying nanodiamonds to drug delivery. We’ve talked to a lot of clinicians and described nanodiamonds and what they can do. I ask, ‘Is that useful to you?’ They reply, ‘Yes, by all means.’”

For their study, Ho and his team used living murine macrophage cells, human colorectal carcinoma cells and doxorubicin hydrochloride, a widely used chemotherapy drug. The drug was successfully loaded onto the nanodiamond clusters, which efficiently ferried the drug inside the cells. Once inside, the clusters broke up and slowly released the drug.

In the genetic studies, the researchers exposed cells to the bare nanodiamonds (no drug was present) and analyzed three genes associated with inflammation and one gene for apoptosis, or cell death, to see how the cells reacted to the foreign material. Looking into the circuitry of the cell, they found no toxicity or inflammation long term and a lack of cell death. In fact, the cells grew well in the presence of the nanodiamond material.

Developing a modular, nanoparticle drug delivery system

There are two aspects to creating an effective drug: finding a chemical compound that has the desired biological effect and minimal side-effects and then delivering it to the right place in the body for it to do its job.

With the support from a $478,000, five-year CAREER award from the National Science Foundation, Eva Harth is tackling the second part of this problem. She is creating a modular, multi-functional drug delivery system that promises simultaneously to enhance the effectiveness and reduce undesirable side-effects of a number of different drugs.

Harth has taken a different approach from other researchers working on nanotechnology for drug development. Instead of trying to encapsulate drugs in nanoscale containers, she decided to create a nanoparticle that had a large number of surface sites where drug molecules could be attached. To do so, she adopted a method that uses extensive internal cross-linking to scrunch a long, linear molecule into a sphere about 10 nanometers in diameter, about the size of a protein. Nanoparticles like this are called nanosponges.

Hamm studies G proteins, arguably the most important signaling molecules in the cell. Scientists think that many diseases, including diabetes and certain forms of pituitary cancer, are caused by malfunctioning G proteins. She and Harth are collaborating on using the transporter to deliver peptides produced by G proteins that disrupt signaling pathways.

“Eva’s methods for drug delivery are very novel and versatile and can be adapted to delivery of proteins, peptides, DNA and smaller chemical compounds like most drugs. The breadth of applications makes her technology very powerful,” Hamm says.

She is now working with Hallahan to adapt her delivery system to carry cisplatinum, a traditional chemotherapy agent that is used to treat a number of different kinds of cancer but is highly toxic and has a number of unpleasant side effects.

By delivering the anti-cancer agent directly to the cancerous tissues, Eva’s system decreases the adverse effects on other tissues and increases its potency by delivering a higher concentration of the drug directly on the cancer, Hallahan explains.

“The people in my lab have tried at a number of different drug delivery systems and Eva’s works the best of those we’ve looked at,” Hallahan says.

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.

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."

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