title: Cell-specific targeting of nanoparticles by multivalent attachment of small molecules.
abstract: 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.
authors.affiliation: Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, Bldg. 149, 13th Street, Room 5403, Charlestown, Massachusetts 02129, USA. weissleder@helix.mgh.harvard.edu
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
authors.forename: Kimberly
authors.initials: K
authors.lastname: Kelly
authors.forename: Eric Yi
authors.initials: EY
authors.lastname: Sun
authors.forename: Timur
authors.initials: T
authors.lastname: Shtatland
authors.forename: Lee
authors.initials: L
authors.lastname: Josephson
mesh_terms: D000818:Animals; D001698:Biomedical Engineering / Q000379:methods*; D001709:Biotechnology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002469:Cell Separation; D016503:Drug Delivery Systems; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D015723:Gene Library; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D049329:Nanostructures; D036103:Nanotechnology / Q000379:methods*; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000378:metabolism; D010641:Phenotype