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已发表论文

双官能 c(RGDyK) 修饰的 Pluronic 胶束被用于血管生成抑制及耐药肿瘤治疗

 

Authors Chen YZ, Zhang W, Huang YK, Gao F, Fang XL
Published Date July 2015 Volume 2015:10 Pages 4863—4881
DOI http://dx.doi.org/10.2147/IJN.S86827
Received 17 April 2015, Accepted 28 May 2015, Published 30 July 2015

Peer reviewers approved by Dr Govarthanan Muthusamy

Approved for publication by Dr Lei Yang

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


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