Delivery of chemotherapeutic drugs in tumour cell-derived microparticles

Nat Commun. 2012;3:1282. doi: 10.1038/ncomms2282.

Abstract

Cellular microparticles are vesicular plasma membrane fragments with a diameter of 100-1,000 nanometres that are shed by cells in response to various physiological and artificial stimuli. Here we demonstrate that tumour cell-derived microparticles can be used as vectors to deliver chemotherapeutic drugs. We show that tumour cells incubated with chemotherapeutic drugs package these drugs into microparticles, which can be collected and used to effectively kill tumour cells in murine tumour models without typical side effects. We describe several mechanisms involved in this process, including uptake of drug-containing microparticles by tumour cells, synthesis of additional drug-packaging microparticles by these cells that contribute to the cytotoxic effect and the inhibition of drug efflux from tumour cells. This study highlights a novel drug delivery strategy with potential clinical application.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / therapeutic use
  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • Cell-Derived Microparticles / metabolism*
  • Cisplatin / administration & dosage
  • Cisplatin / therapeutic use
  • Drug Carriers / metabolism*
  • Female
  • Liver Neoplasms / drug therapy
  • Methotrexate / administration & dosage
  • Methotrexate / therapeutic use
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Neoplasms / drug therapy*
  • Neoplasms, Experimental
  • Ovarian Neoplasms / drug therapy

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Cisplatin
  • Methotrexate