Polymer-drug conjugates for combination anticancer therapy: investigating the mechanism of action

J Med Chem. 2009 Oct 22;52(20):6499-502. doi: 10.1021/jm900804m.

Abstract

We developed a family of polymer-drug conjugates carrying the combination of the anticancer agent epirubicin (EPI) and nitric oxide (NO). EPI-PEG-(NO)8, carrying the highest content of NO, displayed greater activity in Caco-2 cells while it decreased toxicity against endothelium cells and cardiomyocytes with respect to free EPI. FACS and confocal microscopy confirmed conjugates internalization. Light scattering showed formation of micelle whose size correlated with internalization rate. EPI-PEG-(NO)8 showed increased bioavailability in mice compared to free EPI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols*
  • Biological Transport
  • Cell Line, Tumor
  • Epirubicin / administration & dosage
  • Epirubicin / chemistry*
  • Epirubicin / pharmacokinetics
  • Epirubicin / pharmacology*
  • Humans
  • Lipid Metabolism
  • Mice
  • Nitric Oxide / chemistry*
  • Nitric Oxide / metabolism
  • Polyethylene Glycols / chemistry*
  • Solutions
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Solutions
  • Nitric Oxide
  • Polyethylene Glycols
  • Epirubicin