Oncolytic Virus‐Like Nanoparticles for Tumor‐Specific Gene Delivery

Abstract Nucleic acid drugs are widely used in biomedical fields. However, one of the main challenges in vivo is to selectively deliver nucleic acid drugs to subcellular compartments. To solve this problem, an oncolytic virus‐like nanoparticle, OV@FN, is constructed that can directly deliver nucleic acids to the cytoplasm through membrane fusion in response to the slightly acidic environment of the tumor. OV@FN is composed of a nano‐core (NA‐Zn@G) that can accurately release nucleic acids in response to high concentrations of glutathione in the cytoplasm of tumor cells and a hybrid membrane vesicle (FN) expressing oncolytic virus fusion membrane glycoprotein (mVSV‐G). The study findings suggest that OV@FN efficiently and selectively delivers nucleic acids to the cytoplasm of tumor cells, as compared to normal cells. Importantly, FN effectively induces tumor cells to form a syncytium, thus promoting intracellular drug diffusion, and enhancing the gene therapy effect. In vivo gene silencing test shows that OV siR @FN has a significant nucleic acid delivery performance. In the melanoma model, the OV 3pdsR @FN shows remarkable tumor ablation ability and improves the immunosuppressive microenvironment of the tumor site. OV@FN offers a novel approach to designing gene delivery and tumor therapy platforms.