In vivo tumor cell targeting with "click" nanoparticles.

  • von Maltzahn G
  • Ren Y
 et al. 
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Abstract

The in vivo fate of nanomaterials strongly determines their biomedical efficacy. Accordingly, much effort has been invested into the development of library screening methods to select targeting ligands for a diversity of sites in vivo. Still, broad application of chemical and biological screens to the in vivo targeting of nanomaterials requires ligand attachment chemistries that are generalizable, efficient, covalent, orthogonal to diverse biochemical libraries, applicable under aqueous conditions, and stable in in vivo environments. To date, the copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition or "click" reaction has shown considerable promise as a method for developing targeted nanomaterials in vitro. Here, we investigate the utility of "click" chemistry for the in vivo targeting of inorganic nanoparticles to tumors. We find that "click" chemistry allows cyclic LyP-1 targeting peptides to be specifically linked to azido-nanoparticles and to direct their binding to p32-expressing tumor cells in vitro. Moreover, "click" nanoparticles are able to stably circulate for hours in vivo following intravenous administration (>5 h circulation time), extravasate into tumors, and penetrate the tumor interstitium to specifically bind p32-expressing cells in tumors. In the future, in vivo use of "click" nanomaterials should expedite the progression from ligand discovery to in vivo evaluation and diversify approaches toward multifunctional nanoparticle development.

Author-supplied keywords

  • Alkynes
  • Alkynes: chemistry
  • Amines
  • Amines: chemistry
  • Amino Acid Sequence
  • Animals
  • Azides
  • Azides: chemistry
  • Cattle
  • Cell Line
  • Cyclic
  • Cyclic: chemistry
  • Cyclic: metabolism
  • Cyclic: therapeutic use
  • Fluorescence
  • Gene Expression Regulation
  • Humans
  • Magnetics
  • Mice
  • Mitochondrial Proteins
  • Mitochondrial Proteins: metabolism
  • Nanoparticles
  • Nanoparticles: chemistry
  • Nanoparticles: therapeutic use
  • Neoplasms
  • Neoplasms: drug therapy
  • Neoplasms: metabolism
  • Peptides
  • Polymers
  • Polymers: chemistry
  • Sensitivity and Specificity
  • Sulfhydryl Compounds
  • Sulfhydryl Compounds: chemistry
  • Tumor

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Authors

  • Geoffrey von Maltzahn

  • Geoffrey von Maltzahn

  • Yin Ren

  • Yin Ren

  • Ji-Ho Park

  • Ji-Ho Park

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