Amphiphilic Copolymeric Micelles for Doxorubicin and Curcumin Co-delivery to Reverse Multidrug Resistance in Breast Cancer
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)(PEG2k-PLA5k)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 ATP activity.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.
multidrug resistance amphiphilic polymeric micelles chemosensitizer co-delivery breast cancer
Li Lv Kaifeng Qiu Xiaoxia Yu Chuxiong Chen Fengchao Qin Yonghui Shi Jiebin Ou Tao Zhang Hua Zhu Junyan Wu Guocheng Li Chunxia Liu
Department of Pharmacy,Sun Yat-Sen Memorial Hospital,Sun Yat-Sen University,Guangzhou 510120,Guangdo Department of Pharmacy,Sun Yat-Sen Memorial Hospital,Sun Yat-Sen University,Guangzhou 510120,Guangdo Department of Pharmacy,Sun Yat-Sen Memorial Hospital,Sun Yat-Sen University,Guangzhou 510120,Guangdo
国内会议
广州
英文
1-27
2016-12-17（万方平台首次上网日期，不代表论文的发表时间）