HPMA copolymer-anticancer drug conjugates: design, activity, and mechanism of action.
The design, synthesis and properties of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers as carriers of anticancer drugs are reviewed. Macromolecular therapeutics based on HPMA copolymers are biocompatible, preferentially accumulate in tumors, and possess a higher anticancer efficacy than low molecular weight drugs. Novel designs of HPMA copolymer carriers resulted in long-circulating conjugates and gene and oligonucleotide delivery systems. HPMA copolymer based macromolecular therapeutics were active against numerous cancer models and are in clinical trials. The data obtained indicated that macromolecular therapeutics activated different signaling pathways and possessed a different mechanism of action than free drugs. This bodes well for the success of future research aimed at identification of new intracellular molecular targets as a basis for the design of the second generation of macromolecular therapeutics.
Kopecek
J
J
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City UT 84112, USA. jindrich.kopecec@m.cc.utah.edu
Kopecková
P
P
Minko
T
T
Lu
Z
Z
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D001672:Biocompatible Materials; D015195:Drug Design; D015316:Genetic Therapy; D006801:Humans; D008689:Methacrylates; D009369:Neoplasms / Q000188:drug therapy
D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D008689:Methacrylates; C032802:hydroxypropyl methacrylate