New p32/gC1qR Ligands for Targeted Tumor Drug Delivery

Chembiochem. 2016 Apr 1;17(7):570-5. doi: 10.1002/cbic.201500564. Epub 2016 Feb 19.


Cell surface p32, the target of LyP-1 homing peptide, is upregulated in tumors and atherosclerotic plaques and has been widely used as a receptor for systemic delivery of payloads. Here, we identified an improved LyP-1-mimicking peptide (TT1, CKRGARSTC). We used this peptide in a fluorescence polarization-based high-throughput screening of a 50,000-compound chemical library and identified a panel of compounds that bind p32 with low micromolar affinity. Among the hits identified in the screen, two compounds were shown to specifically bind to p32 in multiple assays. One of these compounds was chosen for an in vivo study. Nanoparticles surface-functionalized with this compound specifically adhered to surfaces coated with recombinant p32 and, when injected intravenously, homed to p32-expressing breast tumors in mice. This compound provides a lead for the development of p32-targeted affinity ligands that circumvent some of the limitations of peptide-based probes in guided drug delivery.

Keywords: cancer; drug delivery; high-throughput screening; nanoparticles; peptides.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopyridines / chemistry*
  • Aminopyridines / pharmacology
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Breast Neoplasms / drug therapy*
  • Carrier Proteins
  • Cell Line, Tumor
  • Drug Delivery Systems*
  • Ethylenediamines / chemistry*
  • Ethylenediamines / pharmacology
  • Female
  • Humans
  • Ligands
  • Mice
  • Mitochondrial Proteins / administration & dosage*
  • Mitochondrial Proteins / chemistry
  • Mitochondrial Proteins / metabolism
  • Nanoparticles / chemistry
  • Peptides, Cyclic / administration & dosage*


  • 4014008 compound
  • Aminopyridines
  • Antineoplastic Agents
  • C1QBP protein, human
  • Carrier Proteins
  • Ethylenediamines
  • Ligands
  • LyP-1 peptide
  • Mitochondrial Proteins
  • Peptides, Cyclic