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.