载顺铂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  

Preparation of Cisplatin Loaded Nano Targeted Probe and the Experimental Study on the Targeting Ability of NPC Cells in Vitro

作　　者：杨大艳 张敏[1] 李华梅[1] 吴汤娜[1] 张洁[1] 景香香[1] Yang Dayan;Zhang Min;Li Huamei;Wu Tangna;Zhang Jie;Jing Xiangxiang(Department of Ultrasound,Hainan Provincial People＇s Hospital,Haikou,Hainan 570311,China)

机构地区：[1]海南省人民医院超声科,海口市570311

出　　处：《中国超声医学杂志》2018年第9期836-839,共4页Chinese Journal of Ultrasound in Medicine

基　　金：国家自然科学基金(No.81760317;30860270);海南省自然科学基金(No.30854;813208)

摘　　要：目的制备一种可载顺铂(CDDP)并具有叶酸分子靶向性的纳米级超声分子探针,研究其基本特性及体外寻靶能力。方法将CDDP、聚乳酸-羟基乙酸(PLGA)按一定比例溶解在有机溶剂中,采用双乳化法制备载有CDDP的纳米级超声造影剂(PLGA/CDDP),观察测量其基本特性及纳米微粒的包封率、载药量,优化CDDP的最佳剂量。通过聚乙二醇亚胺在PLGA表面连接叶酸(FA)分子后,双乳化法制备出载有CDDP,并具有FA分子靶向功能的纳米微粒(PLGA-Fa/CDDP)。将PLGA/CDDP和PLGA-Fa/CDDP分别作用于体外培养的人鼻咽癌(NPC)细胞株HNE-1(FA受体高表达)和CNE-2(FA受体低表达),观察比较其靶向性。结果成功制备了载有CDDP的纳米微粒PLGA/CDDP,该纳米微粒大小均匀,形态圆整,分散性好,直径分布为533.5nm。进一步将FA分子成功连接于PLGA表面成功制备了具有FA分子靶向功能的纳米微粒PLGA-Fa/CDDP,该纳米微粒与FA受体高表达的人NPC细胞株HNE-1细胞可以靶向结合,而与FA受体低表达的人NPC细胞株CNE-2细胞靶向结合不明显。结论成功制备了一种载有CDDP并具有FA分子靶向的纳米级超声造影剂微粒PLGA-Fa/CDDP,其对人NPC细胞株HNE-1细胞具有明显靶向性。Objective To prepare a nanoscale ultrasonic molecular probe which can carry cisplatin（CDDP）with molecular targeting of folic acid,and to study its basic characteristics and in vitro targeting ability.Methods CDDP,poly lactic-co-glycolic acid（PLGA）were dissolved in a certain proportion in organic solvents,and nano ultrasonic contrast agent（PLGA/CDDP）loaded with CDDP was prepared by double emulsification.Then the basic characteristics,encapsulation efficiency and drug loading of nanoparticles were observed and measured,and the optimum dosage of CDDP was optimized.After the folic acid（FA）was attached to the surface of PLGA by polyethylene glycol imide,the nanoparticles containing CDDP and FA molecular targeting function（PLGA-Fa/CDDP）were prepared by emulsification.PLGA/CDDP and PLGA-Fa/CDDP were respectively applied to cultured human nasopharyngeal carcinoma（NPC）cell line HNE-1（high expression of FA receptor）and CNE-2（FA receptor low expression）in vitro,in order to observe and compare their targeting.Results The nanoparticle PLGA/CDDP containing CDDP was successfully prepared.The size of the nanoparticle is uniform,the morphology is round,the dispersion is good,and the diameter is 533.5 nm.Then the nanoparticle PLGA-Fa/CDDP with FA molecular targeting function was successfully prepared by the successful connection of FA molecules on the surface of PLGA.The nanoparticle could target the binding of NPC cell lines HNE-1 cells with high expression of FA receptors,while the binding of CNE-2 cells in NPC cell lines with low expression of FA receptors was not obvious.Conclusions In this study,a PLGA-Fa/CDDP nanoparticle ultrasound contrast agent containing CDDP and FA targeted molecule was successfully prepared.It has obvious targeting effect on human NPC cell line HNE-1 cell.

关 键 词：叶酸 靶向 纳米 顺铂 超声 

分 类 号：R445.1[医药卫生—影像医学与核医学]