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

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.

• Authors: Huaizhong Pan, Monika Sima, Jiyuan Yang, Jindřich Kopeček
• Journal: Macromolecular bioscience (Macromol Biosci) Vol. 13 Issue 2 Pg. 155-60 (Feb 2013) ISSN: 1616-5195 [Electronic] Germany
• PMID: 23339052 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

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

Topics

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