功能化外泌体重编程免疫细胞与肿瘤细胞之间靶向识别  

Functionalized Exosomes Reprogram the Targeted Recognition Between Immune Cells and Tumor Cells

作　　者：项建 叶邦策[1] 尹斌成[1,2] XIANG Jian;YE Bang-ce;YIN Bin-cheng(State Key Laboratory of Bioreactor Engineering,East China University of Science and Technology,Shanghai 200237,China;School of Chemistry and Chemical Engineering,Shihezi University,Shihezi 832003,China)

机构地区：[1]华东理工大学生物反应器工程国家重点实验室,上海200237 [2]石河子大学化学化工学院,石河子832003

出　　处：《中国生物工程杂志》2023年第10期1-9,共9页China Biotechnology

基　　金：国家自然科学基金(22374047、22134003);中央高校基本科研业务费专项资金资助项目。

摘　　要：目的:通过基因工程技术制备表面展示具有促进膜融合作用的水泡性口炎病毒糖蛋白G(vesicular stomatitis virus glycoprotein,VSVG)的外泌体VSVG-Exos,利用核酸探针介导DNA杂交链式反应在其膜表面修饰靶向树突状细胞间黏附分子-3-结合非整合素DC-SIGN的核酸适配体,构建功能化外泌体,通过重编程肿瘤细胞与树突细胞之间的靶向识别过程增强相互作用。方法:以小鼠乳腺癌细胞4T1和小鼠树突状细胞DC2.4为研究对象,通过共聚焦成像和流式细胞术等实验证明VSVG-Exos以膜融合方式特异性结合4T1细胞,以及DC-SIGN适配体具有特异性靶向DC2.4细胞的能力。结果:功能化外泌体可以重编程修饰4T1细胞,增强与DC2.4细胞之间的靶向识别效应。结论:功能化外泌体有效地输送具有特定功能的分子到肿瘤细胞表面,对其进行重编程修饰,提高免疫细胞精准定位和高效攻击肿瘤细胞的能力,为靶向清除肿瘤细胞提供了新的思路和策略。Objective:To prepare the exosomes that display the vesicular stomatitis virus glycoprotein(VSVG)by utilizing genetic engineering technology,which promotes membrane fusion.Meanwhile,the exosomes were further modified with aptamers that target dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin(DC-SIGN)receptors to prepare functionalized exosomes,which is achieved through DNA hybridization chain reaction mediated by nucleic acid probes.This approach reprograms the targeted recognition process between tumor cells and dendritic cells,ultimately enhancing their interaction.Methods:The paper focuses on mouse mammary tumor cells(4T1)and mouse dendritic cells(DC2.4)as research subjects,which demonstrates through confocal imaging and flow cytometry that VSVG-Exos can specifically bind to 4T1 cells via membrane fusion,and that DC-SIGN aptamers can specifically target DC2.4 cells.Results:Functionalized exosomes can reprogram and modify 4T1 cells to enhance their targeted recognition effect with DC2.4 cells.Conclusion:Functionalized exosomes can effectively deliver molecules with specific functions to the surface of tumor cells and reprogram and modify them,thus improving the ability of immune cells to accurately locate and efficiently attack tumor cells.This provides a new approach and strategy for targeted elimination of tumor cells.

关 键 词：功能化外泌体 靶向识别 核酸适配体 膜融合 水泡性口炎病毒糖蛋白 

分 类 号：Q78[生物学—分子生物学]