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Rethinking Nano Drug Design

Research shows that the arrangement of tumor-targeting molecules counts.

Researchers may have made some incorrect assumptions about how to design nanoparticles deliver drugs that target tumor cells, according to preliminary research presented this week at the 2009 Materials Research Society Spring Meeting in San Francisco.

Most of the nanoparticle “envelopes” used to encapsulate cancer drugs rely on two mechanisms to get to their destination. The drugs are coated in these envelopes so that they cannot pass through healthy blood vessels into healthy tissues but can pass through the holes in leaky blood vessels that feed tumors. But this is no guarantee that the tumors will take up the drug, which might continue circulating in the blood. To make the targeting more specific, the outside of these envelopes are often decorated with molecules that are recognized by receptors present in large numbers on the surfaces of tumor cells. Chemists usually load the nanoparticles with these tumor-specific molecules, according MIT chemical engineering professor Paula Hammond, whom I caught up with at the conference. “The assumption is, if you increase the [number of places to bind], you increase the drug uptake,” she says.

But Hammond presented preliminary results suggesting that the number of targeting molecules isn’t the only important factor in getting a tumor to take up a drug; their arrangement is also important. Hammond compared drug uptake when the targeting molecules were loaded all over the nanoparticle envelope, and when they were clustered in patches, as they are on biological cells. “We found that we can greatly influence how much tumors take up by changing the size of the patches, and that drug uptake goes down if there are too many patches.”

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