Synthesis of long-circulating, backbone degradable HPMA copolymer-doxorubicin conjugates and evaluation of molecular-weight-dependent antitumor efficacy

Macromol Biosci. 2013 Feb;13(2):155-60. doi: 10.1002/mabi.201200353. Epub 2013 Jan 22.

Abstract

Backbone degradable, linear, multiblock N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-doxorubicin (DOX) conjugates are synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization followed by chain extension via thiol-ene click reaction. The examination of molecular-weight-dependent antitumor activity toward human ovarian A2780/AD carcinoma in nude mice reveals enhanced activity of multiblock, second-generation, higher molecular weight conjugates when compared with traditional HPMA copolymer-DOX conjugates. The examination of body weight changes during treatment indicates the absence of non-specific adverse effects.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / chemistry*
  • Antibiotics, Antineoplastic / pharmacology*
  • Body Weight / drug effects
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / chemical synthesis
  • Doxorubicin / pharmacology
  • Drug Carriers / chemistry*
  • Drug Carriers / pharmacology
  • Female
  • Humans
  • Mice
  • Mice, Nude
  • Molecular Weight
  • Ovarian Neoplasms / drug therapy
  • Polymethacrylic Acids / chemical synthesis*
  • Polymethacrylic Acids / pharmacology*
  • Structure-Activity Relationship
  • Xenograft Model Antitumor Assays

Substances

  • Antibiotics, Antineoplastic
  • Drug Carriers
  • Polymethacrylic Acids
  • doxorubicin-N-(2-hydroxypropyl)methacrylamide copolymer conjugate
  • Doxorubicin