巨噬细胞膜仿生白蛋白纳米体系的构建及其胶质瘤靶向递药性能评价  

Construction of Macrophage Membrane-Coated Albumin Nanoparticles and Its Drug Delivery Evaluation For Glioma in Vitro

作　　者：张姝月 何美 孙晨 李鹃鹃 丁宝月[3] 丁雪鹰[1] ZHANG Shu-yue;HE Mei;SUN Chen;LI Juan-juan;DING Bao-yue;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;Medical College,Jiaxing University,Jiaxing 314001,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 [3]嘉兴学院医学院,浙江嘉兴314001

出　　处：《中国药学杂志》2022年第8期636-644,共9页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金面上项目资助(81472349);松江区科技攻关项目资助(18sjkjgg);嘉兴市肿瘤光动力靶向药物研究重点实验室资助。

摘　　要：目的构建包载WEE1激酶抑制剂adavosertib的巨噬细胞膜仿生白蛋白纳米粒(MM-BSA/Ada),体外评估其作为胶质瘤靶向递药体系的可行性。方法制备MM-BSA/Ada并筛选最佳膜-核比和最佳药-载比,检测其载体安全性和对C6胶质瘤细胞抗增殖活性,考察其体外细胞摄取、跨血脑屏障转运和跨膜后摄取的能力。结果MM-BSA/Ada具有良好的稳定性,CCK-8结果初步显示,未载药纳米粒在体外细胞实验中对脑血管内皮细胞呈低毒性;与未包膜纳米粒和游离药物相比,MMBSA/Ada给药后的体外抗胶质瘤细胞增殖活性(P<0.001)、胶质瘤细胞摄取量(P<0.001)、体外血脑屏障透过量(P<0.01)及跨膜后摄取量(P<0.001)均显著提高。结论MM-BSA/Ada有较好的胶质瘤靶向递药性能,有望为胶质瘤提供新的放射增敏策略。OBJECTIVE To construct membrane-coated biomimetic albumin nanoparticles loading with WEE1 kinase inhibitor adavosertib(MM-BSA/Ada),and evaluate its glioma drug-targeting feasibility in vitro.METHODS MM-BSA/Ada was prepared and the best mass ratio of membrane/BSA-np and adavosertib/BSA-np was screened.Particle size,Zeta potential,polydispersity index,morphology,and stability of MM-BSA/Ada were characterized.CCK-8 assay was conducted to detect the vector safety in bEnd.3 mouse brain endothelial cells and the anti-proliferation efficiency in C6 rat glioma cells.Its glioma targeting,blood-brain barrier(BBB)penetrating,and cellular uptake after BBB penetrating properties were investigated in vitro.RESULTS MM-BSA/Ada showed good stability,and the CCK-8 results showed that the membrane-coated albumin nanoparticles(MM-BSA)showed low toxicity to bEnd.3 mouse brain endothelial cells in vitro.The in vitro anti-proliferation activity(P<0.001),in vitro cellular uptake capability(P<0.001),in vitro BBB penetration efficiency(P<0.001)and the in vitro cellular uptake ability after BBB penetrating of MMBSA/Ada(P<0.01)were significantly increased when comparing with the uncoated albumin nanoparticles(BSA-np)or free drugs.CONCLUSION MM-BSA/Ada shows good performance in glioma targeting drug delivery,which is expected to provide a new radio-sensitization strategy for glioma.

关 键 词：胶质瘤 adavosertib 细胞膜仿生纳米粒 白蛋白纳米粒 血脑屏障 

分 类 号：R944[医药卫生—药剂学]