Nanotech News

November 7, 2005

Targeting Nanoparticles to Pancreatic Cancer In Vivo

Taking a page from pharmaceutical chemists, researchers at the Massachusetts General Hospital and the Harvard Medical School have created a library of 146 different nanoparticles that they were then able to search for nanoparticles capable of targeting specific cells in the body. Using this approach, the investigators have found a previously undiscovered nanoparticle capable of targeting pancreatic cancer in vivo.

Reporting its work in the journal Nature Biotechnology, a team led by Ralph Weissleder, M.D., and Lee Josephson, Ph.D., describe its use of a robotic chemical synthesis system to create fluorescent and magnetic iron oxide nanoparticles attached to a wide variety of small organic molecules. Approximately 60 copies of each small molecule were attached to any given nanoparticle.

Working with a variety of human cultured cell types, the investigators then screened each of their nanoparticles to see if any were taken up by specific cells. The researchers used fluorescence imaging to determine which, if any, nanoparticles ended up in a particular cell type. The researchers also looked for particular nanoparticles that were not taken up by macrophages, cells that circulate in the blood system and whose function is to remove foreign materials – including nanoparticles – from the body, or by endothelial cells, which line blood vessels and other organs. Designing an imaging agent that avoids endothelial cells helps reduce background noise that can result when non-targeted cells take up an imaging agent.

After identifying two different small-molecule-bearing nanoparticles that were taken up by various human cancer cells but not by macrophages or endothelial cells, the investigators conducted a second experiment to see if either of those nanoparticles could preferentially target cancer cells and be seen in the body using magnetic resonance imaging (MRI). The researchers found that both nanoparticles were taken up specifically by pancreatic tumors in a mouse model of human pancreatic cancer and were readily detected using fluorescence spectroscopy.

The researchers note that they used chemical procedures familiar to any medicinal chemist and that this approach could prove useful for developing nanoparticles targeted to a variety of different types of diseased tissues. They expect that by using these techniques it should be possible to improve the performance of nanomaterials designed to image or deliver drugs to tumors.

This work is detailed in a paper titled, “Cell-specific targeting of nanoparticles by multivalent attachment of small molecules.” This paper was published online in advance of print publication. An abstract is available through the journal’s website.
View abstract.