Dual Functional Peptide-Driven Nanoparticles for Highly Efficient Glioma-Targeting and Drug Codelivery

Mol Pharm. 2016 May 2;13(5):1599-607. doi: 10.1021/acs.molpharmaceut.6b00051. Epub 2016 Apr 18.

Abstract

Compared with peripheral tumors, glioma is very difficult to treat, not only because it has general features of tumor but also because the therapy has been restricted by the brain-blood barrier (BBB). The two main features of tumor growth are angiogenesis and proliferation of tumor cells. RNA interference (RNAi) can downregulate VEGF overexpression to inhibit tumor neovascularization. Meanwhile, doxorubicin (DOX) has been used for cytotoxic chemotherapy to kill tumor cells. Thus, combining RNAi and chemotherapy has been regarded as a potential strategy for cancer treatment. However, the BBB limits the shVEGF-DOX codelivery system to direct into glioma. Here, a smart drug delivery system modified with a dual functional peptide was established, which could target to transferrin receptor (TfR) overexpressing on both the BBB and glioma. It showed that the dual-targeting delivery system had high tumor targeting efficiency in vitro and in vivo.

Keywords: RNA interference; combination therapy; doxorubicin; glioma dual targeting; transferrin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier / metabolism
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / metabolism
  • Cell Line, Tumor
  • Doxorubicin / administration & dosage
  • Drug Delivery Systems / methods
  • Glioma / drug therapy*
  • Glioma / metabolism
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / administration & dosage*
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / metabolism
  • Peptides / administration & dosage*
  • RNA Interference / drug effects
  • Receptors, Transferrin / metabolism
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Peptides
  • Receptors, Transferrin
  • Vascular Endothelial Growth Factor A
  • Doxorubicin