脑胶质瘤靶向的细胞膜仿生递药系统的构建与体外评价  

Construction and in Vitro Study of Glioma-Targeted Cell Membrane Biomimetic Delivery System

作　　者：何美 徐楠 张姝月 李国瑞 丁雪鹰[1] HE Mei;XU Nan;ZHANG Shu-yue;LI Guo-rui;DING Xue-ying(Department of Clinical Pharmacy,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200080,China;Department of Pharmacy,Changhai Hospital,Second Military Medical University,Shanghai 200082,China)

机构地区：[1]上海交通大学附属第一人民医院临床药学科,上海200080 [2]海军军医大学长海医院药学部,上海200082

出　　处：《中国药学杂志》2020年第5期367-374,共8页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金面上项目资助(81472349);上海市科委自然科学基金项目资助(14ZR1433300);上海交通大学医工交叉项目资助(0507N17014);松江区科技攻关项目资助(18Sjkjgg3);国家自然科学基金青年科学基金资助(81703051)。

摘　　要：目的基于肿瘤细胞的同源把向性,拟构建一种脑股质瘤U251细胞膜包覆介孔二氧化娃纳米粒(mesoporous silica nan-oparticles,MSN)的仿生递药系统(U251/MSN),以化疗药物多柔比星(doxorubicin,D0X)为模型药物,初步评价其在胶质瘤靶向治疗中的应用可能。方法使用共挤出法制备U251/MSN-DOX。对纳米粒的粒径、电位、形态进行表征;测定其载药量与包封率;考察纳米粒的细胞毒性、比较包膜前后纳米粒以及不同细胞膜仿生纳米粒在胶质瘤细胞U251中的摄取差异;并通过构建体外血脑屏障(brain-blood barrier,BBB)模型考察仿生纳米粒的跨膜转运效率。结果仿生纳米粒U251/MSN呈球形,可观察到明显的“核壳”结构,粒径为(1:35.70±3.85)nm,载药量为(18.57±2.17)%,包封率为(64.99±2.52)%,细胞实验表明,U251/MSN-DOX细胞毒性低,且较MSN-D0X以及非同源细胞膜纳米粒具备更强的靶向性和跨BBB效率。结论胶质瘤细胞膜可通过共挤出法有效包覆在MSN表面,制备的仿生纳米粒具有良好的靶向性和跨BBB能力,显示出在肿瘤靶向,特别是脑部肿瘤靶向递药领域的应用价值。OBJECTIVE To construct a biomimetic delivery system(U251/MSN-DOX),and assess its application of glioma targeted therapy.METHODS U251 cell membrane was coated on the surface of mesoporous silica nanoparticles(MSN)by co-extrusion to prepare cell membrane biomimetic nanoparticles U251/MSN-DOX.The particle size,potential and morphology were characterized.The physical characteristics,loading content(LC)and encapsulation efficiency(EE)of these nanoparticles were determined.Their toxicity of normal cells was investigated.Their cellular uptake of different formulations in U251 was studied by flow cytometry and fluorescence confocal microscope.Additionally,we assessed the transmembrane transport efficiency of nanoparticles via in vitro BBB.RESULTS The cell membrane-coated nanoparticles U251/MSN were spherical,and a distinct"core-shell"structure could be observed.The particle size was(135.70±3.85)nm,the LC was(18.57±2.17)%,and the EE was(64.99±2.52)%.The cell experiment showed that U251/MSN had low cytotoxicity and U251/MSN-DOX exhibited stronger cellular uptake ability and BBB transporting efficiency.CONCLUSION The glioma cell membrane can be coated on the surface of MSN to construct biomimetic nanoparticles U251/MSN.The biomimetic nanoparticles not only are capable of targeting the homologous tumor cells,but also show the enhanced ability to penetrate BBB,which indicate potential applications in the field of tumor targeted drug delivery especially in brain tumor.

关 键 词：胶质瘤 细胞膜仿生递药系统 介孔二氧化硅纳米粒 血脑屏障 靶向 

分 类 号：R944[医药卫生—药剂学]