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Archive > Volume 33 Issue 2 > 2026,33(2):120-131. DOI:10.3872/j.issn.1007-385X.2026.02.002 Prev Next
Basic Research
Effect and mechanism of folic acid-modified NK cell-derived exosomes delivering reovirus against ovarian cancer
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Abstract:
[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-NKexoReo 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.
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