Reduction/pH dual responsive micelle delivery system for cancer chemo/photothermal /photodynamic therapy

A reduction/pH dual-responsive micelle delivery system encapsulating indocyanine green (ICG) and paclitaxel (PTX) (ICG&PTX@Bio-ss-Mic-DMA) was developed to release loaded drugs programmatically and improve the efficacy of cancer therapy. The hydrophilic end of the polymer amino-polyethylene glycol-disulfide-poly ε-caprolactone (NH₂-PEG-SS-PCL) was modified with 2,3-dimethylmaleic anhydride (DMA) to make it rapidly responsive to the weakly acidic tumor microenvironment (pH 6.5-6.8), inducing charge inversion on the micelle surface and facilitating effective uptake of drug-loaded micelles by cancer cells. Next, the disulfide bonds in the polymers broke and led to the cleavage of the micelles and the release of the loaded drugs in the presence of high levels of glutathione (GSH) in the cytoplasm. ICG&PTX@Bio-ss-Mic-DMA enhanced cellular uptake and cytotoxicity to tumor cells at pH 6.5, while chemo/photothermal/photodynamic therapy synergistically induced apoptosis and necrosis of tumor cells. The results of this study showed that ICG&PTX@Bio-ss-Mic-DMA could realize fluorescence/photothermal imaging-guided cancer chemo/photothermal/photodynamic therapy.