Apoptotic Macrophage-Derived Vesicles Loaded with Oncolytic Virus for Tumor Therapy.

INTRODUCTION: Oncolytic viruses (OVs) represent an emerging modality in cancer immunotherapy, harnessing the ability to selectively infect and lyse cancer cells while eliciting a robust immune response. Despite their promise, the clinical application of OVs is often hindered by the body's innate antiviral defenses, which can neutralize the viruses before they reach tumor sites, and by challenges related to effective penetration and distribution within the tumor microenvironment. METHODS: Apoptotic vesicles were harvested from ultraviolet-induced apoptotic RAW264.7 macrophage cells. Oncolytic adenovirus was loaded into these vesicles via a repeated extrusion method. Physicochemical characterization and viral loading efficiency (via qPCR) were assessed. Cytotoxic effects were evaluated using CCK-8 assays in vitro. RESULTS: Successful encapsulation of the oncolytic adenovirus within the vesicles was achieved, with a high loading efficiency of 84.8%. Compared with free virus, the EV@OA complex exhibited significantly enhanced cytotoxicity against tumor cells. CONCLUSION: Apoptotic macrophage-derived vesicles serve as an effective platform for oncolytic adenovirus delivery, improving anti-tumor efficacy in vitro. Further in vivo validation is warranted.