Pericyte-coverage of human tumor vasculature and nanoparticle permeability

Biol Pharm Bull. 2012;35(5):761-6. doi: 10.1248/bpb.35.761.

Abstract

Nano drug delivery systems (nanoDDS) are a promising strategy for treatment of human tumors. As indicated by our previous work, the extent of pericyte-coverage of tumor vasculature is important to determining nanoDDS efficacy since intratumoral accumulation of nanoDDS is less in tumor models with pericyte-covered vasculature. Here we investigated the clinical relevance of our previous observations in animal models, by determining pericyte coverage using immunohistochemistry of smooth muscle actin (SMA) with CD34: a vascular endothelial marker, in human tumor tissue samples. The investigation revealed that tumor vasculature coverage by pericytes in pancreatic and diffuse-type gastric cancers was significantly greater than in ovarian, colon, and intestinal-type gastric cancers. The latter group of cancers is easier to treat clinically. These observations are consistent with our previous findings in animal models. On the basis of these findings we believe optimization of nanoDDS delivery should be done depend upon a clear understanding of the effects of pericyte vascular coverage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / therapeutic use
  • Drug Delivery Systems*
  • Humans
  • Nanoparticles*
  • Neoplasms / blood supply
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Neovascularization, Pathologic*
  • Pericytes / pathology*
  • Permeability

Substances

  • Antineoplastic Agents