synthesis of ph-sensitive prodrug micelle for site-specifically release of anticancer drugs

Abstract: a novel copolymers based on methyl methacrylate polymer (mma) and methoxy polyethylene glycol (mpeg) with (mpeg)n- b- (pmma)m architecture were synthesized via atom transfer radical polymerization (atrp). subsequent hydrazine reaction with the ester functional group in the copolymer leads to polymers with amine functionalities, which were conjugated with doxorubicin to generate polymer-doxorubicin conjugates. due to the hydrophobicity of the drug conjugated block, the copolymers took on amphiphilic character leading to micelle formation in aqueous solution with an average diameter of 299.6 nm. in vitro release studies demonstrated that this platinum drug delivery system is relatively stable at physiologic conditions but susceptible to mild acidic environments which would trigger the release of conjugated drugs. as an environmentally sensitive drug delivery vehicle, these conjugates can potentially minimize the drug loss during circulation in the blood, where the ph value is neutral, and after reaching the target cell environment, which has a lower ph. this characteristic drug release profile holds the promise to suppress cancer cell chemoresistance by rapidly releasing a high dose of chemotherapy drugs, thereby improving the therapeutic efficacy of the drug payload.