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Cell-specific targeting of nanoparticles by multivalent attachment of small molecules

Nat Biotechnol. 2005 Nov;23(11):1418-23. doi: 10.1038/nbt1159. Epub 2005 Oct 23.

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.

MeSH terms

  • Animals
  • Biomedical Engineering / methods*
  • Biotechnology
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Separation
  • Drug Delivery Systems
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / metabolism
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic*
  • Gene Library
  • Humans
  • Macrophages / metabolism
  • Mice
  • Mice, Nude
  • Nanostructures*
  • Nanotechnology / methods*
  • Neoplasm Transplantation
  • Pancreatic Neoplasms / metabolism
  • Phenotype