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March 29, 2006

Magnetically controlled and triggered nanospheres for precise drug delivery

Nanospheres that are 200 nanometers in diameter, roughly the size of a virus, are used so they won't trigger an immune response in the body. They are also biocompatible so they can be readily absorbed by the cells. It's the structure of the nanospheres that makes drug delivery possible. The spheres have thousands of parallel channels running completely through them. Through capillary action, the spheres can soak up molecules of the drug to be delivered. When the channels are filled, the ends of channels are "capped" to safely seal the drug inside. Once the caps are in place, the nanospheres are "washed" to remove the drug from the outer surface.

The type of material used for the end caps, how they're held in place, and how they're released is the focus of Lin's work. The caps can be dendrimers, biodegradable polymers, genes, proteins, metallic nanoparticles, or semiconductor nanocrystals – also known as quantum dots – and are held in place by chemical bonds. Once the nanospheres are inside the target cells, a trigger is used to pop the caps off and release the drug.

"We're looking at two levels of control," Lin said of the trigger mechanism. "One level is to have the cell control the release and the other would be to control the release externally."

Lin explained that the chemical bond holding the cap in place can be engineered to be unphased by chemicals present in normal cells. However, in cancer cells these chemicals, such as antioxidants, appear in much higher concentrations and would break the bonds on the caps and release the drugs. In this way, only cancer cells could be targeted with powerful chemotherapy drugs .

To achieve external control, Lin is using iron-oxide nanoparticle caps which can be manipulated by a magnetic field. "By using a powerful magnet, we can first concentrate the nanospheres at a particular point, such as a tumor site, and then use the magnetic field to remove the caps and release the drug," Lin said. "The advantage of using a magnetic trigger as opposed to a ultraviolet light trigger is that there's no limit to the depth of tissue we are able to probe … think of an MRI.

By using externally controlled nanospheres, Lin explains that it may be possible to sequentially release genes, chemical markers and other materials within cells in order to track what happens and what specific changes take place. This phase of Lin's research ties into a larger plant metabolomics project at Ames Laboratory.

The end result of this path of nanoscale medical research would be precise delivery of genes and drugs to cells and within cells.

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