Nature Biotechnology 23, 1418 - 1423 (2005)
Published online: 23 October 2005; | doi:10.1038/nbt1159
Cell-specific targeting of nanoparticles by multivalent attachment of small moleculesRalph Weissleder1, Kimberly Kelly1, 2, Eric Yi Sun1, 2, Timur Shtatland1
& Lee Josephson11
Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, Bldg. 149, 13th Street, Room 5403, Charlestown, Massachusetts 02129, USA. 2
These authors contributed equally to this work.
Correspondence should be addressed to weissleder@helix.mgh.harvard.edu Nanomaterials with precise biological functions have considerable potential for use in biomedical applications. Here we investigate whether multivalent attachment of small molecules can increase specific binding affinity and reveal new biological properties of such nanomaterials. We describe the parallel synthesis of a library comprising 146 nanoparticles decorated with different synthetic small molecules. Using fluorescent magnetic nanoparticles, we rapidly screened the library against different cell lines and discovered a series of nanoparticles with high specificity for endothelial cells, activated human macrophages or pancreatic cancer cells. Hits from the last-mentioned screen were shown to target pancreatic cancer in vivo. The method and described materials could facilitate development of functional nanomaterials for applications such as differentiating cell lines, detecting distinct cellular states and targeting specific cell types.
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