Enhanced cytotoxicity of a polymer-drug conjugate with triple payload of paclitaxel

Bioorg Med Chem. 2009 Jul 1;17(13):4327-35. doi: 10.1016/j.bmc.2009.05.028. Epub 2009 May 18.

Abstract

The development of targeting approaches to selectively release chemotherapeutic drugs into malignant tissue is a major challenge in anticancer therapy. We have synthesized an N-(2-hydroxypropyl)-methacrylamide (HPMA) copolymer-drug conjugate with an AB(3) self-immolative dendritic linker. HPMA copolymers are known to accumulate selectively in tumors. The water-soluble polymer-drug conjugate was designed to release a triple payload of the hydrophobic drug paclitaxel as a result of cleavage by the endogenous enzyme cathepsin B. The polymer-drug conjugate exhibited enhanced cytotoxicity on murine prostate adenocarcinoma (TRAMP C2) cells in comparison to a classic monomeric drug-polymer conjugate.

MeSH terms

  • Acrylamides / administration & dosage*
  • Acrylamides / chemistry
  • Adenocarcinoma / drug therapy
  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Dendrimers / administration & dosage*
  • Dendrimers / chemistry
  • Drug Delivery Systems
  • Male
  • Mice
  • Paclitaxel
  • Prodrugs / administration & dosage*
  • Prodrugs / chemistry
  • Prodrugs / therapeutic use
  • Prostatic Neoplasms / drug therapy

Substances

  • Acrylamides
  • Antineoplastic Agents
  • Dendrimers
  • Prodrugs
  • Paclitaxel
  • N-(2-hydroxypropyl)methacrylamide