载竹红菌素纳米靶向探针的制备及其体外对NPC细胞寻靶能力的实验研究  

Experiment study of preparation of homomycin nanoparticle targeting probe and its ability to target NPC cells in vitro

作　　者：王萍[1] 岳文胜[1] 唐雪梅[1] 罗玉群[1] 李祖坤[1] WANG Ping;YUE Wensheng;TANG Xuenei;LUO Yuqun;LI Zukun(Department of Ultrasound, the Affiliated Hospital of North Sichuan Medical College, Sichuan Province, Nanchong 637000, China)

机构地区：[1]川北医学院附属医院超声科

出　　处：《中国医药导报》2019年第19期16-19,33,共5页China Medical Herald

基　　金：四川省教育厅科研计划(17ZB0164)

摘　　要：目的制备一种可载竹红菌素(H)并具有叶酸(FA)分子靶向性的纳米级超声分子探针,探讨其基本特性及体外寻靶能力。方法按一定比例将H、聚乳酸-羟基乙酸共聚物(PLGA)溶解于有机溶剂中,采用双乳化法制备载有H的纳米级超声造影剂(PLGA/H),观察测量PLGA/H的基本特性、包封率及载药量,并优化H的最佳剂量。通过添加偶联叶酸的磷脂DSPE-PEG(2000)Floate在PLGA表面连接FA分子后,采用双乳化法制备出既载有H,又具有FA分子靶向功能的纳米微粒(PLGA-FA/H)。将PLGA/H和PLGA-FA/H分别作用于体外培养的人鼻咽癌(NPC)细胞株CNE2(FA受体高表达)和CNE2(FA受体低表达),观察并比较其靶向性。结果成功制备了载有H的纳米微粒PLGA/H,该纳米微粒的平均粒径为(220.50±91.37)nm,形态圆整,大小均匀且分散性好。PLGA-FA/H纳米微粒可与人NPC细胞株(FA受体高表达)的CNE2细胞靶向结合,而与NPC细胞株(FA受体低表达)的CNE2细胞靶向结合不明显。结论成功制备了一种可载有H且具有FA分子靶向功能的超声造影纳米微粒-PLGA-FA/H,其对人NPC细胞株(FA受体高表达)的CNE2细胞具有靶向性。Objective To prepare a nano-scale ultrasound molecular probe carrying hypocrellin (H) and targeting folic acid (FA) molecule, and to investigate its basic characteristics and in vitro targeting ability. Methods H and polylactic acid-glycolic acid (PLGA) were dissolved in organic solvents in a certain proportion. Nano-scale ultrasound contrast agent (PLGA/H) containing H was prepared by double emulsification method. The basic characteristics, entrapment efficiency and drug loading of PLGA/H were observed and measured, and the optimal dosage of H was optimized. After the FA molecule was attached to the surface of PLGA by adding folate-conjugated phospholipid DSPE-PEG (2000) Floate, nanoparticles with both H and FA molecular targeting function (PLGA-FA) were prepared by double emulsion method. PLGA/H and PLGA-FA/H were respectively applied to human nasopharyngeal carcinoma (NPC) cell lines CNE2 (high expression of FA receptor) and CNE2 (low expression of FA receptor) in vitro to observe and compare their targeting. Results The nanoparticle PLGA/H carrying H was successfully prepared. The average particle size of the nanoparticles was (220.50±91.37) nm, the shape was round, the size was uniform and the dispersion was good. PLGA-FA/H nanoparticles can be targeted to CNE2 cells (high expression of FA receptor) of human NPC cell line, while CNE2 cells (low expression of FA receptor) with NPC cell line have no targeted binding. Conclusion PLGA-FA/H, a kind of contrast-enhanced ultrasound nanoparticle with H and FA molecular targeting function, has been successfully prepared, and it can target CNE2 cells (high expression of FA receptor) of human NPC cell line.

关 键 词：超声 纳米微粒 竹红菌素 叶酸 靶向 

分 类 号：R739.8[医药卫生—肿瘤]