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10/28/2006 8:56:52 AM
Multivalent Nanoparticles Improve Cell Targeting

While a growing body of literature has shown that nanoparticle targeting can improve drug delivery and tumor imaging, there have been few systematic studies examining the net positive effect of nanoparticle targeting. One new study, from members of the MIT-Harvard Center of Cancer Nanotechnology Excellence, tackled that issue head-on and showed just how powerful nanoparticle targeting can be at improving the behavior of nanoparticles in the bloodstream.

Reporting its work in the Journal of Medicinal Chemistry, a research team headed by Lee Josephson, Ph.D., and Ralph Weissleder, M.D., Ph.D., both of Massachusetts General Hospital and Harvard Medical School, showed that coating iron oxide nanoparticles with a peptide known as RGD (named after the three amino acids that form the core of this peptide) increases the half-life of the particles in blood from 13 minutes to 180 minutes. RGD binds to the protein ævß3, which is found on the surface of endothelial cells and on certain types of tumor cells.

In addition, the researchers showed that the presence of multiple RGD peptides acts to increase cell-surface binding in a multiplicative manner in much the same way that the individual loops of Velcro® work together to hold two materials together. This multivalent binding effect leads to the nanoparticles binding more efficiently to tumor cells, which have more ævß3 on their surfaces, than to endothelial cells. The researchers also showed that there is an optimal density of RGD peptides on a nanoparticle surface that correlates with the size of the ævß3 protein. The researchers note that these findings suggest that the use of targeting molecules that are physically smaller than their attached nanoparticles may not be as effective at improving nanoparticle binding to their target cells.

This work, which was supported by the National Cancer Institute, is detailed in a paper titled, “Multivalent effects of RGD peptides obtained by nanoparticle display.” Investigators from the Geneva Hospital in Geneva, Switzerland, and the Vienna Medical School in Vienna, Austria, also participated in this study. An abstract of this paper is available through PubMed.

View abstract.

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