CTLA-4纳米抗体与肿瘤适配体共修饰的双靶向脂质体构建  

Construction of Dual-Targeting Liposomes Co-Modified with CTLA-4 Nanobody and Tumor Aptamer

作　　者：万瑞融[1] 王希斌[1] WAN Ruirong;WANG Xibin(Department of Pharmacy,the First Affiliated Hospital of Guangxi Medical University,Nanning City,Guangxi 530021)

机构地区：[1]广西医科大学第一附属医院药学部,广西南宁市530021

出　　处：《医学理论与实践》2024年第1期5-7,38,共4页The Journal of Medical Theory and Practice

基　　金：广西壮族自治区卫生健康委员会科研课题(Z20200996)。

摘　　要：目的:制备CTLA-4纳米抗体(Nb16)/适配体TLS11a修饰的脂质体,以制备一种能特异性靶向T细胞及肿瘤细胞的双靶向纳米制剂。方法:采用薄膜水化法制备得到纳米脂质体,然后通过化学键的耦联将氨基修饰到脂质体上,TLS11a适配体修饰巯基,Nb16纳米抗体自身带有巯基,将三者进行迈克尔加成反应,即可同时偶联纳米抗体和适配体到脂质体表面,制备得到双靶向脂质体(Nb16-Lipo-TLS11a)。运用透射电镜(TEM)、粒径和电位仪对Nb16-Lipo-TLS11a进行表征,并通过流式细胞术检测其与活化T细胞及肝癌细胞HepG2的结合情况。结果:制备的Nb16-Lipo-TLS11a为椭圆形的脂质体且表现呈均质、分散特征,粒径大小在100nm左右。结合实验结果直接或间接验证了Nb16-Lipo-TLS11a与活化T细胞及肝癌细胞的特异性结合能力。结论:本研究创新性构建的双靶向脂质体,能够特异性结合T细胞和靶细胞,为肿瘤靶向治疗提供了一种新策略。Objective:To prepare a liposome modified by CTLA-4 nanobody(Nb16)/aptamer TLS11a,so as to prepare a dual-target nano-preparation which can specifically target T cells and tumor cells.Methods:We used thin film hydration method to construct liposomes,and the amino group was modified on the liposomes through chemical bond coupling,and the TLS11a aptamers were modified with a sulfhydryl group,and the Nb16 nano-antibody itself was equipped with a sulfhydryl group.By Michael addition reaction,nano-antibody and aptamer can be coupled to the surface of liposome at the same time,and double-targeted liposome(Nb16-Lipo-TLS11a)can be prepared.Nb16-Lipo-TLS11a was characterized by transmission electron microscopy(TEM),particle size and potentiometry,and its binding to activated T cells and hepatocellular carcinoma cells HepG2 was detected by flow cytometry.Results:Nb16-Lipo-TLS11a was an ellipsoidal liposome with homogeneous and dispersed characteristics,and the particle size was around 100nm.The specific binding ability of Nb16-Lipo-TLS11a to activated T cells and hepatocellular carcinoma target cells was directly or indirectly verified by the combined experimental.Conclusion:The innovative construction of dual-targeted liposomes in this study can specifically bind T cells and target cells,providing a new strategy for tumor-targeted therapy.

关 键 词：纳米抗体 适配体 脂质体 双靶向 肝癌 

分 类 号：R73[医药卫生—肿瘤]