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Friday, September 12, 2008

A complex hybrid Nanoparticle slightly smaller than a virus deliver drug cocktail


The nanometer-sized cargo ships look individually like a chocolate-covered nut cluster, in which a biocompatible lipid forms the chocolate shell and magnetic nanoparticles, quantum dots and the drug doxorubicin are the nuts. Credit: Ji-Ho Park, UCSD

Scientists at UC San Diego, UC Santa Barbara and MIT report that their nano-cargo-ship system integrates therapeutic and diagnostic functions into a single device that avoids rapid removal by the body’s natural immune system. It is 50 nanometers in size. So it has three times less volume than the typical virus.


1 nm diameter of glucose molecule
2 nm diameter of DNA helix
5 nm diameter of insulin molecule
6 nm diameter of a hemoglobin molecule
10 nm thickness of cell wall (gram negative bacteria)
75 nm size of typical virus
200 nm diameter of smallest bacteria
1000nm diameter of sperm cell (smallest cell in the human body)



“The idea involves encapsulating imaging agents and drugs into a protective ‘mother ship’ that evades the natural processes that normally would remove these payloads if they were unprotected,” said Michael Sailor, a professor of chemistry and biochemistry at UCSD who headed the team of chemists, biologists and engineers that turned the fanciful concept into reality. “These mother ships are only 50 nanometers in diameter, or 1,000 times smaller than the diameter of a human hair, and are equipped with an array of molecules on their surfaces that enable them to find and penetrate tumor cells in the body.”

These microscopic cargo ships could one day provide the means to more effectively deliver toxic anti-cancer drugs to tumors in high concentrations without negatively impacting other parts of the body.

The researchers designed the hull of the ships to evade detection by constructing them of specially modified lipids--a primary component of the surface of natural cells. The lipids were modified in such a way as to enable them to circulate in the bloodstream for many hours before being eliminated. This was demonstrated by the researchers in a series of experiments with mice.

The researchers loaded their ships with three payloads before injecting them in the mice. Two types of nanoparticles, superparamagnetic iron oxide and fluorescent quantum dots, were placed in the ship’s cargo hold, along with the anti-cancer drug doxorubicin. The iron oxide nanoparticles allow the ships to show up in a Magnetic Resonance Imaging, or MRI, scan, while the quantum dots can be seen with another type of imaging tool, a fluorescence scanner.


This study provides the first example of a single nanomaterial used for simultaneous drug delivery and multimode imaging of diseased tissue in a live animal," said Ji-Ho Park, a graduate student in Sailor's laboratory who was part of the team. Geoffrey von Maltzahn, a graduate student working in Bhatia's laboratory, was also involved in the project, which was financed by a grant from the National Cancer Institute of the National Institutes of Health.

The nano mother ships look individually like a chocolate-covered nut cluster, in which a biocompatible lipid forms the chocolate shell and magnetic nanoparticles, quantum dots and the drug doxorubicin are the nuts. They sail through the bloodstream in groups that, under the electron microscope, look like small, broken strands of pearls.

The researchers are now working on developing ways to chemically treat the exteriors of the nano ships with specific chemical "zip codes," that will allow them to be delivered to specific tumors, organs and other sites in the body.

Thursday, September 4, 2008

Tobacco Mosaic Virus can deliver gene silencing RNA and enables new drugs in weeks


Tobacco mosaic virus is like a 18-nanometer wide straw, which can hold gene silencing RNA

The tobacco mosaic virus appears to be the key to safe and effective delivery of gene silencing RNA.

Bentley's team has successfully hollowed out the virus and filled it with siRNA, and then used it to slip the frail substance into all sorts of cells, from kidney tissue to cancer. The researchers have proven that the tiny capsules provide adequate protection, and that they release their payloads once inside -- hitting their target genes right on the mark.

The short, double-stranded RNA molecules known as siRNA can program cells to destroy disease-causing proteins. Their molecules turn on a cell's own built-in disease-fighting mechanisms. They can be programmed for a wide range of ailments -- from cancers to viruses -- and because they use the cell's own defense mechanisms, they produce minimal side effects.

In addition to treating cancers and genetic disorders, siRNA could prove useful against a variety of rare diseases that have, and always will be, overlooked by big pharmaceutical companies -- the long tail of disease.

People suffering from similar, exotic maladies could band together and recruit a small team of scientists, as if they were the Seven Samurai, to champion their cause and quickly design a cure.

“The speed with which you develop siRNA drugs is truly amazing,” said Stephen Hyde. “In the past, a traditional small molecule drug might take several years of intensive research effort by a large team of scientists to develop. Today, with siRNA technology, it is possible for a single researcher to develop a drug candidate in a few weeks.”

Bentley is optimistic that the virus will not cause health problems because most people already have traces of it in their blood -- from second-hand smoke -- and it does not seem to cause irritation or obvious immune-system problems.

Protecting the payload is not the only challenge, said Ben Berkhout, a biotechnology expert at the University of Amsterdam. Even if the delicate molecules are packaged in the perfect substance, they still need some sort of a guidance system.

"You want to efficiently get the siRNA drug into the cells where the therapeutic action should be,” said Berkhout.

By coating each tube with special proteins that can recognize and penetrate cancer cells, Bentley's team hopes to make smart drugs that will only go where they are needed.

If that trick works, tobacco may finally be able to turn over a new leaf.