Recently, polymer drug conjugates (PDCs) have attracted considerable attention in the treatment of cancer. In this work, a simple strategy has been developed to make PDCs of an antitumor alkylating agent, chlorambucil, using a biocompatible disulphide linker. Chlorambucil-based chain transfer agent was used to prepare various homopolymers and block copolymers in a controlled fashion via reversible addition-fragmentation chain transfer polymerization. Chlorambucil conjugated block copolymer, poly(polyethylene glycol monomethyl ether methacrylate)-b-poly(methyl methacrylate), formed nanoaggregates in aqueous solutions, which are characterized by dynamic light scattering and field emission-scanning electron microscopy. Finally, the simplicity of the design is exemplified by performing a release study of chlorambucil under reducing condition by using D,L-dithiothreitol.
Keywords: RAFT polymerization; antitumor alkylating agents; chlorambucil; prodrugs; self-assembly.
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