文献类型：期刊文献

中文题名：工程化外泌体介导巨噬细胞清除肿瘤外泌体

英文题名：Clearance of Tumor Exosomes by Engineered Exosomes-assisted Phagocytosis of Macrophages

作者：王璐[1];陈梦丽[1];何芳[1,2];项建[1];尹斌成[1,2,3];叶邦策[1,2]

机构：[1]华东理工大学生物反应器国家重点实验室,上海200237;[2]浙江工业大学药学院长三角绿色制药协同创新中心,杭州310032;[3]石河子大学化学化工学院,石河子832003

年份：2022

卷号：42

期号：6

起止页码：1

中文期刊名：中国生物工程杂志

外文期刊名：China Biotechnology

收录：CSTPCD;;北大核心:【北大核心2020】；CSCD:【CSCD2021_2022】；

基金：国家自然科学基金(21822402、22134003);浙江省自然科学基金联合基金(LHDMZ22H300008)资助项目。

语种：中文

中文关键词：工程化外泌体;肿瘤外泌体;表皮生长因子受体;白细胞介素-8;吞噬

外文关键词：Engineered exosomes(enExos);Tumor exosomes;Epidermal growth factor receptor;Interleukin-8;Phagocytosis

摘要：目的:通过膜表面修饰改造技术构建工程化外泌体(engineered exosomes,enExos),并以此介导巨噬细胞特异性清除膜表面富含表皮生长因子受体(epidermal growth factor receptor,EGFR)的肿瘤外泌体。方法:利用表面展示技术获得膜表面展示趋化因子(chemokine 8,CXCL8)的外泌体,同时在其磷脂双分子层上修饰EGFR核酸适配体制备工程化外泌体;纳米颗粒跟踪和纳米粒度电位分析enExos的尺寸、电位;CCK-8试剂盒检测细胞活力;透射电子显微镜观察enExos与高表达EGFR的肿瘤外泌体的特异性结合;荧光成像技术及流式细胞术分析探究enExos靶向趋化巨噬细胞吞噬高表达EGFR的肿瘤外泌体。结果:成功构建膜表面展示EGFR与CXCL8的工程化外泌体,enExos可以特异性识别并捕获高表达EGFR的肿瘤外泌体,同时利用其趋化因子CXCL8特异性靶向巨噬细胞膜表面趋化因子受体CXCR1/CXCR2,刺激巨噬细胞对肿瘤外泌体的捕获及清除。结论:工程化外泌体促进了特定肿瘤外泌体的清除,为后续深入研究工程化外泌体抑制癌症转移的作用奠定基础,并期望为癌症转移治疗提供新的研究方向。
Objective:This paper aims to construct engineered exosomes(enExos)by membrane surface modification technology,and use enExos to mediate the removal of epidermal growth factor receptor(EGFR)-rich tumor exosomes on the membrane surface by macrophages.Methods:The exosomes displaying the chemokine 8(CXCL8)on the membrane surface were obtained by surface display technology.Meanwhile,the EGFR nucleic acid aptamer was modified on the CXCL8-expressing exosomes to prepare enExos.The size and potential of enExos were analyzed by nanoparticle tracking analysis and nanoparticle size potentiometer.Cell viability was measured by CCK-8 assay.The specific binding of enExos to EGFR-expressing tumor exosomes was observed by transmission electron microscopy.Finally,the phagocytosis of tumor exosomes with high EGFR expression by enExos-targeted chemotactic macrophages was detected by fluorescence imaging and flow cytometry.Results:The enExos with EGFR and CXCL8 displayed on the membrane surface were successfully constructed.enExos can specifically recognize and capture tumor exosomes with high EGFR expression,and at the same time use their chemokine CXCL8 to specifically target the macrophage membrane.Surface chemokine receptors CXCR1/CXCR2 stimulate the capture and clearance of tumor exosomes by macrophages.Conclusion:enExos promote the clearance of specific tumor exosomes,laying a foundation for the subsequent in-depth study of their role in inhibiting cancer metastasis,and they are expected to provide new research directions for cancer metastasis therapy.