Abstract
Multiple drug resistance (MDR) seriously reduces the efficacy of many chemotherapeutic agents for cancer. P-Glycoprotein, an efflux pump overexpressed on the cell surface, plays an important role in drug resistance, but several surfactants, such as vitamin E TPGS, can inhibit P-glycoprotein. In this study, a polylactide-surfactant block copolymer poly(l-lactide)-vitamin E TPGS (PLA-TPGS) was synthesized using bidentate sulfonamide zinc ethyl complex as an efficient catalyst, and its self-assembled nanoparticles were used as carriers of doxorubicin. We first found that the activity of P-glycoprotein in drug-resistant breast cancer MCF-7/ADR cells was decreased after incubation with PLA-TPGS nanoparticles. In addition, the nuclear accumulation and cytotoxicity of doxorubicin were significantly increased by encapsulation into the nanoparticles. The enhanced efficacy of the doxorubicin-loaded PLA-TPGS nanoparticles may result from the combination of inhibition of efflux and increased entry of doxorubicin into the nucleus in drug-resistant MCF-7/ADR cells. Therefore, this innovative delivery system has potential to act as a nanomedicine for therapy of both drug-sensitive and drug-resistant cancer.
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