Macromolecular therapeutics in cancer treatment: the EPR effect and beyond

J Control Release. 2012 Dec 10;164(2):138-44. doi: 10.1016/j.jconrel.2012.04.038. Epub 2012 May 1.


In this review, I have discussed various issues of the cancer drug targeting primarily related to the EPR (enhanced permeability and retention) effect, which utilized nanomedicine or macromolecular drugs. The content goes back to the development of the first polymer-protein conjugate anticancer agent SMANCS and development of the arterial infusion in Lipiodol formulation into the tumor feeding artery (hepatic artery for hepatoma). The brief account on the EPR effect and its definition, factors involved, heterogeneity, and various methods of augmentation of the EPR effect, which showed remarkably improved clinical outcomes are also discussed. Various obstacles involved in drug developments and commercialization are also discussed through my personal experience and recollections.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Drug Delivery Systems*
  • Drug and Narcotic Control
  • Ethiodized Oil / administration & dosage
  • Humans
  • Marketing
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Permeability
  • Polymers / administration & dosage


  • Antineoplastic Agents
  • Polymers
  • Ethiodized Oil