Chen Yanzuo, Zhang Wei, Huang Yukun, Gao Feng, Fang Xiaoling
Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology, Fudan University, Shanghai, People's Republic of China ; Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, School of Pharmacy, Fudan University, Shanghai, People's Republic of China.
Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, School of Pharmacy, Fudan University, Shanghai, People's Republic of China ; CONRAD, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Arlington, VA, USA.
Int J Nanomedicine. 2015 Jul 30;10:4863-81. doi: 10.2147/IJN.S86827. eCollection 2015.
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.
通过用普朗尼克聚合物胶束（c[RGDyK]-FP-DP）修饰c(RGDyK)（环RGD[精氨酸-甘氨酸-天冬氨酸]肽）开发了双功能药物递送系统，以克服化疗药物跨血肿瘤屏障转运率低和多药耐药（MDR）肿瘤治疗效果差的缺点。c(RGDyK)能够以高亲和力和特异性与在肿瘤血管内皮细胞和肿瘤细胞部位大量表达的整合素蛋白结合，将其与普朗尼克F127嵌段共聚物的N-羟基琥珀酰亚胺活化的PEO末端偶联。在本研究中，用c(RGDyK)-FP-DP处理后，观察到MDR癌细胞中肿瘤血管生成减少和凋亡活性增加。对c(RGDyK)-FP-DP的形态、粒径、zeta电位和药物释放进行了全面表征。重要的是，体外抗血管生成结果表明，c(RGDyK)-FP-DP对人脐静脉内皮细胞的管状形成具有显著抑制作用，并促进了MDR KBv细胞中的细胞凋亡活性。此外，与其他对照组相比，c(RGDyK)-FP-DP明显提高了KBv肿瘤球体穿越血肿瘤屏障后的生长抑制效果。结果表明，c(RGDyK)修饰的普朗尼克聚合物胶束可对人脐静脉内皮细胞和KBv MDR癌细胞同时发挥药理作用，产生类似于我们体外细胞研究中观察到的双功能抗癌效果。
