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

Yanzuo Chen,1,2 Wei Zhang,2,3 Yukun Huang,1 Feng Gao,1 Xiaoling Fang2 1Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology, 2Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, School of Pharmacy, Fudan University, Shanghai, People&...

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Autores principales:	Chen YZ, Zhang W, Huang YK, Gao F, Fang XL
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/98983de7c2d1432680f34f4864eb34a6
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spelling	oai:doaj.org-article:98983de7c2d1432680f34f4864eb34a62021-12-02T02:56:05ZDual-functional c(RGDyK)-decorated Pluronic micelles designed for antiangiogenesis and the treatment of drug-resistant tumor1178-2013https://doaj.org/article/98983de7c2d1432680f34f4864eb34a62015-07-01T00:00:00Zhttp://www.dovepress.com/dual-functional-crgdyk-decorated-pluronic-micelles-designed-for-antian-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yanzuo Chen,1,2 Wei Zhang,2,3 Yukun Huang,1 Feng Gao,1 Xiaoling Fang2 1Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology, 2Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, School of Pharmacy, Fudan University, Shanghai, People’s Republic of China; 3CONRAD, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Arlington, VA, USA Abstract: 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. Keywords: dual-functional, micelles, c(RGDyK), antiangiogenesis, multidrug resistanceChen YZZhang WHuang YKGao FFang XLDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 4863-4881 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Chen YZ Zhang W Huang YK Gao F Fang XL Dual-functional c(RGDyK)-decorated Pluronic micelles designed for antiangiogenesis and the treatment of drug-resistant tumor
description	Yanzuo Chen,1,2 Wei Zhang,2,3 Yukun Huang,1 Feng Gao,1 Xiaoling Fang2 1Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology, 2Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, School of Pharmacy, Fudan University, Shanghai, People’s Republic of China; 3CONRAD, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Arlington, VA, USA Abstract: 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. Keywords: dual-functional, micelles, c(RGDyK), antiangiogenesis, multidrug resistance
format	article
author	Chen YZ Zhang W Huang YK Gao F Fang XL
author_facet	Chen YZ Zhang W Huang YK Gao F Fang XL
author_sort	Chen YZ
title	Dual-functional c(RGDyK)-decorated Pluronic micelles designed for antiangiogenesis and the treatment of drug-resistant tumor
title_short	Dual-functional c(RGDyK)-decorated Pluronic micelles designed for antiangiogenesis and the treatment of drug-resistant tumor
title_full	Dual-functional c(RGDyK)-decorated Pluronic micelles designed for antiangiogenesis and the treatment of drug-resistant tumor
title_fullStr	Dual-functional c(RGDyK)-decorated Pluronic micelles designed for antiangiogenesis and the treatment of drug-resistant tumor
title_full_unstemmed	Dual-functional c(RGDyK)-decorated Pluronic micelles designed for antiangiogenesis and the treatment of drug-resistant tumor
title_sort	dual-functional c(rgdyk)-decorated pluronic micelles designed for antiangiogenesis and the treatment of drug-resistant tumor
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/98983de7c2d1432680f34f4864eb34a6
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Dual-functional c(RGDyK)-decorated Pluronic micelles designed for antiangiogenesis and the treatment of drug-resistant tumor

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