title: 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: Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah 84112, USA.
authors: Huaizhong
authors: H
authors: Pan
authors: Monika
authors: M
authors: Sima
authors: Jiyuan
authors: J
authors: Yang
authors: Jindřich
authors: J
authors: Kopeček
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry* / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry* / Q000494:pharmacology; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008970:Molecular Weight; D010051:Ovarian Neoplasms / Q000188:drug therapy; D011109:Polymethacrylic Acids / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D011109:Polymethacrylic Acids; C055176:doxorubicin-N-(2-hydroxypropyl)methacrylamide copolymer conjugate; D004317:Doxorubicin