主动靶向乳腺癌的pH响应纳米粒子的构建及体外评价

发布时间：2018-04-03 18:03

本文选题：纳米医学　切入点：聚多巴胺　出处：《第二军医大学学报》2017年06期

【摘要】：目的制备主动靶向乳腺癌的pH响应负载多烯紫杉醇(docetaxel,DTX)的纳米粒子,并考察其理化性质、载药和药物缓释特征及对人乳腺癌MCF-7细胞的靶向和杀伤效果。方法采用纳米沉淀法和基于聚多巴胺(polydopamine,PDA)的表面修饰方法制备主动靶向MCF-7细胞的载DTX的叶酸(folic acid,FA)和PDA修饰的胆酸-聚乳酸-羟基乙酸共聚物纳米粒子(DTX-loaded CA-PLGA@PDA-PEG-FA/NPs);采用透射电镜观察纳米粒子的形貌,纳米粒度仪分析纳米粒子的粒径和zeta电位,X射线光电子能谱仪(XPS)分析纳米粒子表面修饰情况;采用透析法和高效液相色谱法研究纳米粒子的载药率、包封率以及体外释放曲线;采用激光扫描共聚焦显微镜和流式细胞仪分析负载荧光探针的纳米粒子的体外细胞摄取;采用MTT法研究载药纳米粒子对MCF-7细胞的存活率的影响。结果本研究制备的DTX-loaded CA-PLGA@PDA-PEG-FA/NPs呈"核-壳"结构,水合粒径为(166.4±3.9)nm,zeta电位为(-11.7±3.8)mV,载药量为(9.67±0.45)%,包封率为(88.32±3.10)%,在pH 5.0的释放介质中药物释放较在pH7.4的释放介质中快,XPS分析结果显示PDA和叶酸在纳米粒子表面的修饰,MCF-7细胞摄取的主动靶向的纳米粒子多于未连接主动靶向配体的纳米粒子,载药主动靶向纳米粒子的细胞毒性明显优于DTX的临床制剂泰素帝○R。结论主动靶向乳腺癌的pH响应的载药纳米粒子表现出良好的主动靶向性和MCF-7细胞杀伤效果。
[Abstract]:Objective to prepare active targeting breast cancer response to load pH docetaxel (docetaxel, DTX) nanoparticles, and investigate its physicochemical properties, drug loading and drug release characteristics of MCF-7 human breast cancer cell targeting and killing effect. Methods by nanoprecipitation method and based on poly dopamine (polydopamine PDA), surface modification method for preparing active targeting of MCF-7 cells containing DTX folic acid (folic acid, FA) and PDA modified acid - PLGA nanoparticles (DTX-loaded CA-PLGA@PDA-PEG-FA/NPs); to observe the morphology of nano particles by transmission electron microscopy, nano particle size analyzer and zeta potential of the particle size X, X-ray photoelectron spectroscopy (XPS) analysis of surface modified nanoparticles; by dialysis and HPLC study nanoparticles drug loading, encapsulation efficiency and in vitro release curve using confocal laser scanning; Cell uptake in vitro confocal microscopy and flow cytometry analysis of nanoparticles fluorescent probe; using a MTT method of drug loaded nanoparticles on MCF-7 cell survival rate. Results of the research on the preparation of DTX-loaded CA-PLGA@PDA-PEG-FA/NPs was "core-shell" structure, hydrated particle size (166.4 + 3.9) nm, zeta potential (-11.7 + 3.8) mV, loading (9.67 + 0.45)%, entrapment rate (88.32 + 3.10)% in the pH 5 release medium of drug release in pH7.4 release medium, XPS analysis showed that PDA and folic acid on the surface of nanoparticles modified active target uptake in MCF-7 cells to the nanoparticles than not connected active targeting ligands targeting drug loaded nanoparticles, preparation of Taxotere, clinical R. conclusion the cytotoxicity of nanoparticles was significantly higher than that of DTX active targeting breast cancer pH response of drug loaded nano particles exhibit good Active targeting and MCF-7 cell killing effect.

【作者单位】：清华大学生命科学学院生物学系;清华大学深圳研究生院生命与健康学部基因与抗体治疗重点实验室;中山大学药学院(深圳)药剂学系;新加坡国立大学工程学院化学与生物分子工程系;
【基金】：国家自然科学基金(31270019) 广东杰出青年科学基金(2014A030306036) 广东省科技计划项目(2016A020217001) 广东省培养高层次人才特殊支持计划(201428030) 深圳市科技计划基础研究项目(JCYJ20160531195129079,JCYJ20150430163009479,JCYJ20140417115840285,JCYJ20160428182427603,JCYJ20160301152300347,JCYJ20150529164918738)~~
【分类号】：R943

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