Synthesis of Long‐Circulating, Backbone Degradable HPMA Copolymer–Doxorubicin Conjugates and Evaluation of Molecular‐Weight‐Dependent Antitumor Efficacy

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.