Amphiphilic Copolymeric Micelles for Doxorubicin and Curcumin Co-delivery to Reverse Multidrug Resistance in Breast Cancer
作者单位：中山大学孙逸仙纪念医院药学部 Department of PharmacyZengcheng District People's Hospital of Guangzhou Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene RegulationSun Yat-Sen Memorial HospitalSun Yat-Sen University
会议名称：《2017年广东省药师周大会》
会议日期：2017年
学科分类：100702[医学-药剂学] 1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100602[医学-中西医结合临床] 10[医学]
基 金：supported by Guangdong Natural Science Foundation (NO.2014A030310394) Grant 163 from Key Laboratory of Malignant Tumor Molecular Mechanism and Translational Medicine of Guangzhou Bureau of Science and Information Technology
关 键 词：multidrug resistance amphiphilic polymeric micelles chemosensitizer co-delivery breast cancer
摘 要：Development of multidrug resistance against chemotherapeutic drugs is one of the major obstacles to successful cancer therapy in the clinic. Thus far, amphiphilic polymeric micelles and chemosensitizers have been used to overcome multidrug resistance in cancer. The goals of this study were to prepare poly(ethylene glycol)-bock-poly(lactide)(PEG-PLA) micelles for co-delivery of the chemotherapeutic drug doxorubicin(DOX) with a chemosensitizer curcumin(CUR), investigate the potential of the dual drug-loaded micelles((DOX+CUR)-Micelles) to reverse multidrug resistance, and explore the underlying mechanisms.(DOX+CUR)-Micelles were prepared using an emulsion solvent evaporation method. The cellular uptake, drug efflux, down-regulation of P-glycoprotein expression and inhibition of ATP activity of(DOX+CUR)-Micelles were studied in drug-resistant MCF-7/ADR cells. In vitro analyses demonstrated that(DOX+CUR)-Micelles were superior to free DOX, free drug combination(DOX+CUR), and DOX-loaded micelles in inhibiting proliferation of MCF-7/ADR cells. This effect of(DOX+CUR)-Micelles was partially attributable to their highest cellular uptake, lowest efflux rate of DOX, and strongest effects on down-regulation of P-glycoprotein and inhibition of ATPactivity. Additionally,(DOX+CUR)-Micelles showed increased tumor accumulation and strong inhibitory effect on tumor growth in the xenograft model of drug-resistant MCF-7/ADR cells compared to that of other drug formulations. These results indicate that(DOX+CUR)-Micelles display potential for application in the therapy of drug-resistant breast carcinoma.