文献类型：期刊文献

英文题名：Incorporation of drug efflux inhibitor and chemotherapeutic agent into an inorganic/organic platform for the effective treatment of multidrug resistant breast cancer

作者：Dong, Yang[1];Liao, Hongze[2];Yu, Jian[1];Fu, Hao[1];Zhao, De[1];Gong, Ke[1];Wang, Qi[3];Duan, Yourong[1]

机构：[1]Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, State Key Lab Oncogenes & Related Genes,Shanghai, Shanghai 200032, Peoples R China;[2]Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Marine Drugs Res Ctr,Dept Pharm,State Key Lab Onc, Shanghai 200127, Peoples R China;[3]East China Univ Sci & Technol, Sch Chem & Mol Engn, Shanghai Key Lab Funct Mat Chem, Key Lab Adv Mat & Inst Fine Chem, Shanghai 200237, Peoples R China

年份：2019

卷号：17

期号：1

外文期刊名：JOURNAL OF NANOBIOTECHNOLOGY

收录：;EI(收录号：20195307944895);WOS:【SCI-EXPANDED(收录号:WOS:000514598300003)】；

基金：The authors acknowledge financial support from the National Natural Science Foundation of China (No. 81602718, No. 81771839, No. 81572999 and No. 81773272), the State Key Laboratory of Oncogenes and Related Genes (No.91-17-20). Medical-Engineering Joint Funds from Shanghai Jiao Tong University (No. YG2017QN43), Shanghai Municipal Commission of Health and Family Planning (No. 20174Y0123).

语种：英文

外文关键词：Codelivery; MDR; Inorganic/organic; Verapamil; Novantrone

摘要：Background Multidrug resistance (MDR) is a pressing obstacle in clinical chemotherapy for breast cancer. Based on the fact that the drug efflux is an important factor in MDR, we designed a codelivery system to guide the drug efflux inhibitor verapamil (VRP) and the chemotherapeutic agent novantrone (NVT) synergistically into breast cancer cells to reverse MDR. Results This co-delivery system consists of following components: the active targeting peptide RGD, an inorganic calcium phosphate (CaP) shell and an organic inner core. VRP and NVT were loaded into CaP shell and phosphatidylserine polyethylene glycol (PS-PEG) core of nanoparticles (NPs) separately to obtain NVT- and VRP-loaded NPs (NV@CaP-RGD). These codelivered NPs allowed VRP to prevent the efflux of NVT from breast cancer cells by competitively combining with drug efflux pumps. Additionally, NV@CaP-RGD was effectively internalized into breast cancer cells by precise delivery through the effects of the active targeting peptides RGD and EPR. The pH-triggered profile of CaP was also able to assist the NPs to successfully escape from lysosomes, leading to a greatly increased effective intracellular drug concentration. Conclusion The concurrent administration of VRP and NVT by organic/inorganic NPs is a promising therapeutic approach to reverse MDR in breast cancer.