Effect and mechanism of folic acid-modified NK cell-derived exosomes delivering reovirus against ovarian cancer

YE Rui1,2; DAI Xiaofeng3; LIU Xiong1; CHEN Liang4; ZHANG Jing5; ZHANG Yingchun5; GUO Ting6; ZHAO Xing1,2

Return

Effect and mechanism of folic acid-modified NK cell-derived exosomes delivering reovirus against ovarian cancer

VernacularTitle: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
Author: YE Rui1,2 ^{1
,

2
,

3
,

4
,

5
,

6} ; DAI Xiaofeng3 ^{1
,

2
,

3
,

4
,

5
,

6} ; LIU Xiong1 ^{1
,

2
,

3
,

4
,

5
,

6} ; CHEN Liang4 ^{1
,

2
,

3
,

4
,

5
,

6} ; ZHANG Jing5 ^{1
,

2
,

3
,

4
,

5
,

6} ; ZHANG Yingchun5 ^{1
,

2
,

3
,

4
,

5
,

6} ; GUO Ting6 ^{1
,

2
,

3
,

4
,

5
,

6} ; ZHAO Xing1,2 ^{1
,

2
,

3
,

4
,

5
,

6}
Author Information

1. Tissue Engineering and Stem Cell Experimental Center, Guizhou Medical University, Guiyang 550000, Guizhou, China;
2. Department of Immunology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang 550000, Guizhou, China;
3. National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China;
4. Department of Thoracic and Breast Surgery, Anshun People’s Hospital, Anshun 561000, Guizhou, China;
5. Department of Biology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang 550000, Guizhou, China;
6. Department of Obstetrics and Gynecology, Affiliated Hospital of Guizhou Medical University, Guiyang 550000, Guizhou, China
Publication Type:Journal Article
Keywords: 卵巢癌；自然杀伤细胞；外泌体；呼肠孤病毒；叶酸受体-α
From: Chinese Journal of Cancer Biotherapy 2026;33(2):120-131
CountryChina
Language:Chinese
Abstract: [摘要] 目的：开发新型溶瘤呼肠孤病毒（Reo）递送系统，以克服中和抗体对Reo的中和作用并提升其肿瘤靶向性。方法：通过切向流过滤联合超高速离心法制备自然杀伤细胞外泌体（NKexo），叶酸（FA）修饰后采用挤压法包载Reo，构建FA-NKexo-Reo递送系统；通过透射电镜（TEM）、纳米粒径分析、蛋白质印迹（WB）法、核磁共振氢谱及流式细胞术等技术表征其理化性质；采用CCK-8、流式细胞术、Transwell实验及激光共聚焦显微镜评估FA-NKexo-Reo递送系统体外细胞毒性及细胞摄取能力；通过人卵巢癌裸鼠皮下移植瘤模型评价FA-NKexo-Reo的肿瘤靶向性、疗效及安全性。结果：FA-NKexo-Reo粒径为（94.0 ± 28.5）nm，Zeta电位为（-21.26 ± 1.57）mV，包封率达（49.7 ± 15.6）%；在中和抗体的存在下，FA-NKexo-Reo对卵巢癌细胞SKOV3和A2780仍可表现出显著的细胞毒性（P < 0.01）；荷瘤鼠活体成像显示FA-NKexo-Reo肿瘤靶向性显著优于NKexo组，肿瘤抑制率提升60%（P < 0.001）。结论：成功制备FA-NKexo-Reo递送系统，在中和抗体的存在下，FA-NKexo-Reo可保护并靶向递送Reo到高表达叶酸受体的卵巢癌细胞，从而增强Reo的抗肿瘤作用。