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Reduction-sensitive mixed micelles assembled from amphiphilic prodrugs for self-codelivery of DOX and DTX with synergistic cancer therapy

Wu, Jilian, Zhang, Huiyuan, Hu, Xu, Liu, Ruiling, Jiang, Wei, Li, Zhonghao, Luan, Yuxia
Colloids and Surfaces B: Biointerfaces 2018 v.161 pp. 449-456
biodegradability, colloids, cytotoxicity, disulfide bonds, doxorubicin, ethylene glycol, micelles, neoplasm cells, neoplasms, polyethylene glycol, surfactants, therapeutics, water solubility
Clinically, codelivery of chemotherapeutics has been limited by poor water-solubility and severe systemic toxicity. In this work, we developed a new reduction-sensitive mixed micellar system for self-codelivery of doxorubicin (DOX) and docetaxel (DTX). Biodegradable methoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) was coupled with DOX and DTX by a reduction-sensitive disulfide bond, resulting in mPEG-PCL-SS-DOX and mPEG-PCL-SS-DTX, respectively. mPEG-PCL-SS-DOX was mixed with mPEG-PCL-SS-DTX at a mole ratio of 1:1 in water, forming a mixed micellar system. The mixed micelles had a diameter of 223.7nm and a low critical micelle concentration. Reductive-triggered drug release revealed a “smart” characteristic of the mixed micelles. A cellular uptake and cytotoxicity assay in vitro showed that the mixed micelles could efficiently accumulate in MCF-7 cells and suppress the growth of tumour cells. The proposed reduction-sensitive mixed micelles assembled from amphiphilic prodrugs can be used as a promising drug codelivery system for cancer therapy.