载顺铂及Fe3O4叶酸靶向多模态探针的制备及体外寻靶能力的实验研究  

Preparation of multi-mode probe loaded with cisplatin and FeO folic acid and its targeting ability in vitro

作　　者：杨大艳 陈其青 钟婷婷 张敏[1] 陈艳 谢琳 景香香[1] 林凌[1] 王明华[2] YANG Da-yan;CHEN Qi-qing;ZHONG Ting-ting;ZHANG Min;CHEN Yan;XIE Lin;JING Xiang-xiang;LIN Ling;WANG Ming-hua(Hainan General Hospital (Affiliated Hainan Hospital of Hainan Medical College), Haikou 570311, Hainan Province, China;The Second Affiliated Hospital of Hainan Medical College, Haikou 570311, Hainan Province, China)

机构地区：[1]海南省人民医院(海南医学院附属海南医院),海南海口570311 [2]海南医学院第二附属医院,海南海口460106

出　　处：《海南医学院学报》2020年第17期1302-1306,共5页Journal of Hainan Medical University

基　　金：国家自然科学基金(81760317、81871365);海南省自然科学基金(818MS126);省重点研发计划项目(ZDYF2019136)。

摘　　要：目的:制备一种包裹液态氟碳(PFP),可载顺铂(CDDP)及四氧化三铁(Fe3O4)并以叶酸修饰的具有分子靶向性的多模态纳米级超声分子探针,研究其基本特性及体外寻靶能力方法:通过聚乙二醇亚胺法在聚乳酸-羟基乙酸(PLGA)表面连接叶酸(Fa)分子,制成靶向膜材料(PLGA-Fa)后,将PLGA-Fa、Fe3O4、CDDP水溶液、PFP按一定比例溶解在有机溶剂中,采用双乳化法制备载有Fe3O4、CDDP、PFP的纳米级靶向多模态超声造影剂(PLGA-Fa/Fe3O4/CDDP/PFP),观察测量其基本特性及纳米微粒的包封率、载药量,将靶向PFFCP和非靶向PFCP分别作用于体外培养的人鼻咽癌(NPC)细胞株HNE-1,观察其靶向性。结果:成功制备了载有Fe3O4、CDDP、PFP的纳米级靶向多模态超声造影剂(PLGA-Fa/Fe3O4/CDDP/PFP),该纳米微粒大小均匀,形态圆整,分散性好,直径分布为204 nm,平均电位为-15 MV,该靶向纳米微粒与Fa受体高表达的人NPC细胞株HNE-1细胞结合率较非靶向纳米粒明显增高。结论:本研究成功制备了一种载Fe3O4、CDDP、PFP的纳米级靶向多模态超声造影剂(PLGA-Fa/Fe3O4/CDDP/PFP),该纳米粒对人NPC细胞株HNE-1细胞具有明显靶向性。Objective To prepare a multimodal nanoscale ultrasonic molecular probes encapsulated with liquid fluorocarbon,capable of carrying cisplatin(CDDP),Fe3O4 and possessing the property of molecular targeting modified with folic acid,and to explore its basic characteristics and in vitro targeting ability.Methods PLGA-Fa was made by attaching the folic acid(Fa)molecule to the surface of PLGA.Fe3O4,CDDP and PFP were dissolved in organic solvents in a certain proportion and a nanoscale targeted multimodal ultrasound contrast agent was prepared(PLGA-Fa/Fe3O4/CDDP/PFP)by double emulsion technique,containing Fe3O4,CDDP and PFP.The basic properties,encapsulation efficiency and drug loading of nanoparticle were measured to evaluate the optimal dosage of CDDP;the target PFCP and non-target PFCP were applied in in vitro human nasopharyngeal carcinoma(NPC)cell line HNE-1(high expression of Fa receptor)for determination of its targeting ability.Results The nanoscale targeted multimodal ultrasound contrast agent(PLGA-Fa/Fe3O/CDDP/PFP)was successfully prepared with an uniform size and good dispersion.The diameter was 204 nm,and the average electric potential was-15 MV.The target nanoparticle could bind to human NPC cell line HNE-1 more significantly compared with the non-target one.Conclusion In this study,a nanoscale targeted multimodal ultrasound contrast agent PLGA-Fa/Fe3O4/CDDP/PFP containing Fe3O4,CDDP and PFP is successfully prepared.The nanoparticle has the potential of targeting HNE-1 cells.

关 键 词：叶酸 靶向 顺铂 超声 

分 类 号：R943[医药卫生—药剂学]