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.
Developing an intelligent drug delivery/release system, which can transport drugs to the target tissues precisely and release drugs timely, is an important challenge in chemotherapy. A multistage sensitive drug delivery system is designed by inserting a folate (FA) modified lipid and a pH/temperature dual‐sensitive amphiphilic copolymer into a liposome bilayer. The stretchable copolymer plays a role in protection on FA ligand for more accurate targeting. Then, the stretch ability of the copolymer in the liposome bilayer is verified by using the Langmuir–Blodgett film technique. The interaction between the 1,2‐dipalmitoyl‐sn‐glycerol‐3‐phosphocholine (DPPC) monolayer and hybrid liposomes is found to increase, indicating the FA ligand is exposed due to the copolymer shrinking with increasing temperature. Fluorescence polarization measurements demonstrate that the insertion of the copolymer improves the stability of the liposome and offers pH‐controllability for drug release. As a result, the drug leakage of the hybrid liposome is restrained significantly at pH 7.4, while at an acidic pH, the drug release is accelerated. The designed pH/temperature dual‐sensitive copolymer is expected to provide more precise targeting and environmentally controlled drug release to drug delivery systems based on liposomes.
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