中国肿瘤生物治疗杂志2026，Vol.33Issue(2)：120-131,12.DOI:10.3872/j.issn.1007-385x.2026.02.002
叶酸修饰的NK细胞外泌体递送呼肠孤病毒抗卵巢癌的作用及机制
Effect and mechanism of folic acid-modified NK cell-derived exosomes delivering reovirus against ovarian cancer
摘要
Abstract
Objective:To develop a novel delivery system for oncolytic reovirus(Reo)to circumvent neutralization by anti-Reo antibodies and enhance tumor-targeting efficiency.Methods:Natural killer cell-derived exosomes(NKexo)were prepared via tangential flow filtration combined with ultracentrifugation.After folic acid(FA)modification,Reo was encapsulated into NKexo using an extrusion method to construct the FA-NKexo-Reo delivery system.The physicochemical properties of FA-NKexo-Reo were characterized by transmission electron microscopy(TEM),nanoparticle tracking analysis,Western blot,proton nuclear magnetic resonance spectroscopy,and flow cytometry.The in vitro cytotoxicity and cellular uptake of FA-NKexo-Reo was evaluated using CCK-8 assays,flow cytometry,Transwell assays,and confocal laser microscopy.A human ovarian cancer xenograft model in nude mice was established to assess the tumor-targeting capability,therapeutic efficacy,and treatment safety of FA-NKexo-Reo.Results:FA-NKexo-Reo exhibited an average particle size of(94.0±28.5)nm and a zeta potential of(-21.26±1.57)mV,with an encapsulation efficiency of(49.7±15.6)％.In the presence of neutralizing antibodies,FA-NKexo-Reo retained significant cytotoxicity against SKOV3 and A2780 ovarian cancer cells(P＜0.01).In vivo fluorescence imaging demonstrated superior tumor-targeting capability of FA-NKexo-Reo compared to NKexo,with a 60％increase in tumor suppression rate(P＜0.001).Conclusion:The FA-NKexo-Reo delivery system was successfully prepared.In the presence of neutralizing antibodies,FA-NKexo-Reo effectively protects and selectively delivers Reo to ovarian cancer cells with high folate receptor expression,significantly enhancing the antitumor efficacy of Reo.关键词
卵巢癌/自然杀伤细胞/外泌体/呼肠孤病毒/叶酸受体-αKey words
ovarian cancer(OC)/natural killer(NK)cell/exosome/reovirus/folate receptor-α(FR-α)分类
医药卫生引用本文复制引用
叶瑞,戴晓峰,刘雄,陈亮,张晶,张迎春,郭婷,赵星..叶酸修饰的NK细胞外泌体递送呼肠孤病毒抗卵巢癌的作用及机制[J].中国肿瘤生物治疗杂志,2026,33(2):120-131,12.基金项目
国家自然科学基金(82060564,82460604) （82060564,82460604）
贵州省科技厅重点科技计划[黔科合基础-ZK(2021)012号] （2021）
贵州医科大学肿瘤免疫治疗技术工程研究中心项目[校工程中心,2024(001)] （001）
贵州省卫生健康委员会科技基金(gzwkj2022-087) （gzwkj2022-087）
