双配体修饰脂质聚合物杂化纳米粒的制备及细胞摄取研究  

Preparation and the in vitro cell uptake of lipid-polymer hybrid nanoparticles modified with double ligand

作　　者：曾诚[1,2] 许芳 杨晓艺[1,2] 侯亚申[1] 李建光 ZENG Cheng;XU Fang;YANG Xiaoyi;HOU Yashen;LI Jianguang(Xinjiang Medical University,Urumqi 830011,China;Xinjiang Institute of Materia Medica,Urumqi 830004,China)

机构地区：[1]新疆医科大学,乌鲁木齐830011 [2]新疆维吾尔自治区药物研究所,乌鲁木齐830004

出　　处：《西北药学杂志》2020年第2期243-248,共6页Northwest Pharmaceutical Journal

基　　金：省部共建中亚高发病成因与防治国家重点实验室开放课题项目(编号:SKL-HIDCA-2018-11);新疆维吾尔自治区科技支疆项目(编号:2018E02069);新疆医科大学研究生创新创业项目(编号:CXCY2018044);新疆医科大学研究生创新创业项目(编号:CXCY2018008);新疆维吾尔自治区研究生科研创新项目(编号:XJ2019G188)。

摘　　要：目的制备双修饰的主动心肌靶向的载荧光探针香豆素-6(C-6)的脂质-聚合物杂化纳米粒(LPHNs),并考察其细胞摄取。方法通过巯基化反应,合成导向化合物心肌细胞靶向肽-聚乙二醇-磷脂酰乙醇胺(PCM-PEG-DSPE)。选取C-6为荧光探针,采用自动组装法制备包载C-6的LPHNs,再通过插入法,用PCM和细胞穿膜肽(TAT)对C-6-LPHNs进行修饰。以心肌细胞(H9C2)为模型做体外细胞摄取实验。结果双修饰的C-6-LPHNs的平均粒径为74.5±4.2 nm,分散系数(PDI)为0.051±0.013,Zeta电位为-32.8±1.2 mV,包封率为87.04%±3.19%。双修饰的C-6-LPHNs对H9C2心肌细胞的摄取率明显高于未修饰的C-6-LPHNs。结论LPHNs经双修饰后可促进H9C2心肌细胞的摄取。Objective To prepare active myocardial-targeted carrier via use of primary cardiomyocyte(PCM)and trans-activating transcriptional activator(TAT)-modified coumarin-6(C-6)containing lipid-polymer hybrid nanoparticles(LPHNs),and to investigate their cellular uptake.Methods A directional compound PCM-PEG-DSPE was synthesized by a thiolation reaction.C-6 was selected as the fluorescent probe,and the LPHNs encapsulating C-6 were prepared by automatic assembly method.Then C-6-LPHNs were modified by the method of insertion with PCM and TAT.The in vitro cell uptake assays were performed by using cardiomyocytes(H9C2)as a model.Results The average particle size of the double-modified C-6-LPHNs was 74.5±4.2 nm,the dispersion coefficient(PDI)was 0.051±0.013,the Zeta potential was-32.8±1.2 mV,and the encapsulation efficiency was 87.04%±3.19%.The uptake rate of H9C2 cardiomyocytes in double-modified C-6-LPHNs group was significantly higher than that of unmodified C-6-LPHNs group.Conclusion LPHNs can promote the uptake of H9C2 cardiomyocytes via double modification.

关 键 词：香豆素-6 脂质聚合物杂化纳米粒 心肌细胞靶向肽 细胞穿膜肽 细胞摄取 

分 类 号：R944[医药卫生—药剂学]