Synthesis of Long-Circulating, Backbone Degradable HPMA CopolymerDoxorubicin Conjugates and Evaluation of Molecular-Weight-Dependent Antitumor Efficacy

Backbone degradable, linear, multiblock N-(2-hydroxypropyl)methacrylamide (HPMA) copolymerdoxorubicin (DOX) conjugates are synthesized by reversible additionfragmentation 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 copolymerDOX conjugates. The examination of body weight changes during treatment indicates the absence of non-specific adverse effects.