Abstract
Utilization of nitrogen mustards as anticancer drugs opened the way for precise cancer chemotherapy owing to their ability to cross-link deoxyribonucleic acid (DNA). However, the non-specificity and lower water solubility limit their aptitude to behave as effective anticancer drugs. Herein we embed the clinically approved nitrogen mustard, chlorambucil (CBL), into a redox-responsive polymeric vector to overcome those bottlenecks as well as to achieve better efficacy. We have synthesized amphiphilic diblock copolymers (BCPs) consisting of polymerized segments of a pendent disulfide-labeled CBL prodrug monomer and hydrophilic 2-(dimethylamino)ethyl methacrylate monomer via reversible addition–fragmentation chain transfer polymerization. The well-defined polyprodrug amphiphiles with CBL loading content >40 wt% could form uniform micelles with an average diameter of 45–110 nm through a macromolecular self-assembly strategy. For the release of caged CBL, disassembly of the self-assembled micelles was attained ...
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