Here we demonstrate a type of pH and redox dual-responsive micelles, which were self-assembled in aqueous solution by an amphiphilic polymer, methoxypoly(ethylene glycol)-cystamine-poly(L-glutamic acid)-imidazole (mPEG-SS-PGA-IM). Considering tumor cells or tissues exhibiting low pH values and high glutathione (GSH) concentration, mPEG-SS-PGA-IM micelles possessed the charge conversion at pH of tumor tissues, which can facilitate cellular uptake of tumor cells. Furthermore, mPEG-SS-PGA-IM micelles can escape from endo/lysosomes based on the proton sponge effect, following degraded by higher concentration of GSH in cytoplasm. CLSM images of HCT116 cells indicated that mPEG-SS-PGA-IM micelles can escape from endo/lysosomes and enter cytoplasm. MTT assay showed that (paclitaxel) PTX-loaded mPEG-SS-PGA-IM micelles had higher cytotoxicity against HCT116 cells compared with PTX-loaded mPEG-PBLG and mPEG-SS-PBLG micelles. These results indicated that these mPEG-SS-PGA-IM micelles, as novel and effective pH- and redox-responsive nanocarriers, have great potential to both improve drug targeting efficiency while also enhancing the antitumor efficacy of PTX.
Keywords: charge conversion; dual-responsive; paclitaxel; proton sponge effect.