Reduction and temperature dually-triggered size-shrinkage and drug release of micelles for synergistic photothermal-chemotherapy of cancer

Reduction and temperature dually responsive poly(2-(2-methoxyethoxy)ethylmethacrylate-co-oligo(ethylene glycol) methacrylate)-b-poly(e-caprolactone)-SS-poly(e-caprolactone)-b-poly(2-(2-methoxyethoxy)ethylmethacrylat-co-oligo(ethylene glycol) methacrylate) (P(MEO2MA-co-OEGMA)-b-PCL-SS-PCL-b-P(MEO2MA-co-OEGMA)) was synthesized by the combination of ring-opening polymerization (ROP) and atom transfer radical polymerization (ATRP). The copolymer can self-assemble into spherical micelles. After loading doxorubicin (DOX) and photothermal agent Indocyanine green (ICG), the micelles were endowed with synergistic effect of chemotherapy and photothermal therapy to cancer through reduction and temperature dually triggered size-shrinkage and drug release. The micelles showed good reduction and temperature responsiveness due to the presence of disulfide bond and thermoresponsive segments in copolymer. Under reducing conditions, the disulfide bond broke and the micelles were converted into micelles with half the original size, which was conducive to drug release. Near Infrared light (NIR) promoted the photothermal conversion of ICG, so that the micelle underwent a temperature response transition and further promoted the release of drugs. The micelles showed drug release rate, high photothermal conversion efficiency, highly cytotoxic to cancer cells and excellent synergistic photothermal-chemotherapy effect.