文献类型：期刊文献

英文题名：Dual-functional c(RGDyK)-decorated Pluronic micelles designed for antiangiogenesis and the treatment of drug-resistant tumor

作者：Chen, Yanzuo[1,2,3];Zhang, Wei[2,3,4];Huang, Yukun[1];Gao, Feng[1];Fang, Xiaoling[2,3]

机构：[1]E China Univ Sci & Technol, Sch Pharm, Dept Pharmaceut, Shanghai 200237, Peoples R China;[2]Fudan Univ, Sch Pharm, Key Lab Smart Drug Delivery, Minist Educ, Shanghai 200433, Peoples R China;[3]Fudan Univ, Sch Pharm, PLA, Shanghai 200433, Peoples R China;[4]Eastern Virginia Med Sch, Dept Obstet & Gynecol, CONRARAD, Arlington, VA USA

年份：2015

卷号：10

外文期刊名：INTERNATIONAL JOURNAL OF NANOMEDICINE

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000358783600001)】；

基金：This work was sponsored by National Natural Science Foundation of China (30901862), Postdoctoral Science Foundation of China (2014M550222), Shanghai Postdoctoral Sustentation Fund (14R21410500), National Basic Research Program of China (2013CB932500), and the Fundamental Research Funds for the Central Universities (22A201514055 ECUST). The authors also acknowledge the support from School of Pharmacy, Fudan University and the Open Project Program of Key Lab of Smart Drug Delivery (Fudan University), Ministry of Education (SDD2014-2), and State Key Laboratory of Molecular Engineering of Polymers (Fudan University) (K2015-15).

语种：英文

外文关键词：dual-functional; micelles; c(RGDyK); antiangiogenesis; multidrug resistance

摘要：Dual-functional drug delivery system was developed by decorating c(RGDyK) (cyclic RGD [arginine-glycine-aspartic acid] peptide) with Pluronic polymeric micelles (c[RGDyK]FP- DP) to overcome the drawbacks of low transport of chemotherapeutics across the blood-tumor barrier and poor multidrug-resistant (MDR) tumor therapy. c(RGDyK) that can bind to the integrin protein richly expressed at the site of tumor vascular endothelial cells and tumor cells with high affinity and specificity was conjugated to the N-hydroxysuccinimide-activated PEO terminus of the Pluronic F127 block copolymer. In this study, decreased tumor angiogenic and increased apoptotic activity in MDR cancer cells were observed after the treatment with c(RGDyK)-FP-DP. c(RGDyK)-FP-DP was fully characterized in terms of morphology, particle size, zeta potential, and drug release. Importantly, in vitro antiangiogenesis results demonstrated that c(RGDyK)-FP-DP had a significant inhibition effect on the tubular formation of human umbilical vein endothelial cells and promoted cellular apoptotic activity in MDR KBv cells. In addition, the growth inhibition efficacy of KBv tumor spheroids after crossing the blood-tumor barrier was obviously increased by c(RGDyK)-FP-DP compared to other control groups. Results suggested that c(RGDyK)-decorated Pluronic polymeric micelles can take pharmacological action on both human umbilical vein endothelial cells and KBv MDR cancer cells, resulting in a dual-functional anticancer effect similar to that observed in our in vitro cellular studies.