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Caltech Team Attacks Tumors with Nanotechnology

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A team of researchers from the California Institute of Technology recently provided the first evidence that targeted nanoparticles can be used safely and effectively in the clinic. Led by Mark Davis, a professor of chemical engineering at Caltech, the researchers demonstrated a method in which small siRNA strands are packaged into a self-assembling nanoparticle, constructed of polymers, that then delivers the siRNA strands to the tumor and turns off a critical cancer gene. The nanoparticles can be directly injected into a patient's bloodstream and then expelled through urine. The team also provided the first evidence that this new type of approach can treat human tumors in a dose-dependent fashion, since a higher number of nanoparticles introduced into the body results in a higher number of nanoparticles in the tumor cells.

The method is currently being evaluated in a Phase I clinical trial sponsored by Calando Pharmaceuticals that began in May 2008. While the trial looks promising, Davis says that getting over the hurdle of trepidation surrounding nanotechnology in the clinic is no small task. "A lot of the challenges with being able to take something into the clinic [are], of course, having the quality control necessary to get into humans," Davis says. "These [nanoscale] systems are complex, and ours is no different in the sense that we have multiple polymers, a protein and RNA, so usually with any new technology, the higher the complexity, the higher the risk factor and the more nervousness you have when people try to take it into the clinic."

Ultimately, Davis says that the potential versatility of their nano-delivery system will trump any misgivings clinicians and patients might have about its safety or efficacy. "This is a very modular system, so you can stick an antibody on there and make it go to other places and other cancers," he says. "You can also change the sequence of the RNA and attack other genes, so in the cancer area there are many options for doing plug-and-play." His lab is now working on modifying their nanoparticle system to deliver siRNAs through the blood-brain barrier in order to attack neurodegenerative diseases such as Huntington and Parkinson's disease.

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