pH and Temperature Double-Switch Hybrid Micelles for Controllable Drug Release.

pH/temperature dual-responsive hybrid micelles were prepared for constructing a double-locked drug delivery system. The temperature-sensitive polyethylene glycol-poly(tetrahydropyranylmethacrylate)-polyethylene glycol (PEG-PTHPMA-PEG) triblock copolymers were synthesized by reversible addition-fragmentation chain transfer polymerization and amide coupling reaction. pH-sensitive poly(2-(diisopropylamino ethylmethacrylate)-polyethylene glycol (PDPA-PEG) diblock polymers were introduced, which could self-assemble with PEG-PTHPMA-PEG in aqueous solutions to form hybrid micelles. The anticancer drug doxorubicin, which was encapsulated in the core of the hybrid micelles, could be released only under simultaneous stimulations of pH and temperature. It was proved that the micelles could maintain their structural stability under a unilateral stimulus, while the structure collapsed and recombined under a double stimulus, which triggered a large amount of drug release. Furthermore, the excellent biocompatibility and dual sensitivity of the vector were also proved by cytotoxicity experiments. The dual-responsive hybrid micelles designed here showed the advantages of a double insurance lock of drug leakage and precise controllability of drug release, which could act as accurate drug delivery systems.