Stability-tunable core-crosslinked polymeric micelles based on an imidazole-bearing block polymer for pH-responsive drug delivery

Abstract

Polymeric micelles from block copolymers have gained increasing attention in cancer drug delivery. However, the fabrication of polymeric micelles that are stable in biological fluids and unstable at tumor sites remains a principal challenge. To achieve the tunable stability for the polymeric micelles, Zn coordination-induced core-crosslinked polymeric micelles have been proposed and confirmed. Herein, a block copolymer bearing imidazole pendants is synthesized which is capable of self-assembling into polymeric micelles in water. After core-crosslinking, it can be found that the critical micelle concentration (CMC) of the core-crosslinked polymeric micelles is significantly lower than that of non-crosslinked polymeric micelles. Particularly, the drug-loaded core-crosslinked polymeric micelles are fragile and easily affected by the slightly acidic environments, which makes it possible to turn the polymeric micelles back to hydrophilic polymers and therefore disassemble micelles to unload cargoes. The drug-loaded core-crosslinked polymeric micelles display adequate toxicity as a result of their low IC50 value of 3.713 ± 0.166 μg/mL. Collectively, Zn coordination-induced core-crosslinked polymeric micelles offer a design idea for practicable drug delivery system in cancer therapy.