A Novel Oncolytic Virus Formulation Based on Mesenchymal Stem Cell-Derived Vesicles for Tumor Therapy.

Developing new drug delivery systems is crucial for enhancing the efficacy of oncolytic virus (OV) therapies in cancer treatment. In this study, mesenchymal stem cell (MSC)-derived vesicles and oncolytic viruses are exploited to construct a novel formulation. It has been hypothesized that vesicle-coated OVs could amplify cytotoxic effects through superior internalization by tumor cells. MSC vesicles possess natural tumor homing ability and biocompatibility, which can enhance the targeting, uptake, and therapeutic effects of OVs on tumor cells. Experimental results indicated that this treatment system has increased the apoptosis of tumor cells. Furthermore, flow cytometry analysis demonstrated that the uptake of tumor cells by OVs coated with MSC vesicles soared away compared to uncoated OVs, being 1.5 times than that of the uncoated group. Additionally, the confocal laser scanning microscopy also showed that the fluorescence intensity within tumor cells pretreated with MSC-coated OVs was greater. Meanwhile, propidium iodide (PI) staining revealed that MSC-coated Ovs exposed to tumor cells accelerating the apoptosis of the latter. According to the statistics, the number of dead cells was increased, and the flow cytometry testified that the apoptosis in the MSC-coated OV group was as high as 23.78%. These findings highlight the potential of MSC vesicle-coated OVs in enhancing the delivery and efficacy of oncolytic virus therapy, providing a promising strategy for cancer treatment.