NIR Activated Upper Critical Solution Temperature Polymeric Micelles for Trimodal Combinational Cancer Therapy

The balance between drug efficiency and its side effects on normal tissues is still a challenging problem to be solved in current cancer therapies. Among different strategies, cancer therapeutic methods based on nanomedicine delivery systems have received extensive attention due to their unique advantages such as improved circulation and reduced toxicity of drugs in the body. Herein, we constructed dual-responsive polymeric micelles DOX&ALS@MFM based on an upper critical solution temperature (UCST) polymer to simultaneously combine chemotherapy, photothermal therapy (PTT), and photodynamic therapy (PDT). Amphiphilic block copolymer P(AAm-co-AN)-b-PEI-ss-PEG-FA with a critical point of 42 °C was able to self-assemble into polymeric micelles under physiological conditions, which further encapsulated anticancer drug doxorubicin (DOX) and photosensitizer ALS to obtain drug-loaded micelles DOX&ALS@MFM. Micelles aggregated at tumor sites due to folate targeting and an enhanced permeability retention (EPR) effect. After that, the high intracellular concentration of glutathione (GSH) and near-infrared (NIR) light prompted disassembly of the polymer to release DOX and ALS. ALS not only plays a role in PTT but also produces singlet oxygen, therefore killing tumor cells by PDT. Both in vitro and in vivo studies demonstrated the photothermal conversion and reactive oxygen species generation ability of DOX&ALS@MFM micelles, at the same time as the excellent inhibitory effect on tumor growth with NIR light irradiation. Thus, our research substantiated a new strategy for the biomedical application of UCST polymers in the cited triple modal tumor therapy.