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Biological Chemistry

Particles Home in on Diseased Cells

Small-molecule-studded nanoparticles find their way to pancreatic cancer cells

by A. Maureen Rouhi
October 31, 2005 | A version of this story appeared in Volume 83, Issue 44

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Nanoparticles decorated with small molecules (model at left). Isatoic anhydride (R = H) or 5-chloroisatoic anhydride (R = Cl) impart affinity for pancreatic cancer cells.
Nanoparticles decorated with small molecules (model at left). Isatoic anhydride (R = H) or 5-chloroisatoic anhydride (R = Cl) impart affinity for pancreatic cancer cells.

BIOTECHNOLOGY

Nanoparticles that reveal pancreatic cancer cells in mice have been developed in the laboratory of Ralph Weissleder at Harvard Medical School. Tools for early detection of pancreatic cancer in humans are lacking, and the nanoparticles may be a step toward better diagnosis of this deadly disease.

Weissleder and coworkers thought that decorating certain fluorescent magnetic nanoparticles"already being used clinically for magnetic resonance imaging"with small molecules would enable the nanoparticles to be taken up selectively by specific cells. The researchers have now shown that this idea works.

For example, nanoparticles studded with isatoic or 5-chloroisatoic anhydride are selectively taken up by pancreatic cancer cells in mice. Their presence inside those cells can be revealed by whole-body fluorescence or magnetic resonance imaging (Nature Biotechnol., published Oct. 23, dx.doi.org/10.1038/nbt1159).

Weissleders approach is novel, says Robert S. Langer, professor of chemical engineering at Massachusetts Institute of Technology. It could lead to a whole new way of targeting cells, he adds.

The work is a step toward giving nanomaterials more biological function—in this case, the ability to access specific cells or biological processes, Weissleder says. One long-term goal is to use materials like these to detect diseases much earlier than currently possible, he adds.

The researchers prepared a library of 146 nanoparticles, each conjugated to an average of 60 copies of a small molecule. Screening revealed 14 with high affinity for pancreatic cancer cells. Among those, the particles decorated with isatoic acid or 5-chloroisatoic acid are poorly taken up by macrophages, which scavenge unmodified nanoparticles, and so were prepared on a large scale for the in vivo studies with mice.

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