Nanoparticle-mediated delivery of oncolytic viral genomes: an innovative strategy for tumor-targeted immunotherapy

Nanoparticle (NP)-mediated delivery of oncolytic viral genomes (vGenomes) represents an innovative strategy to overcome the limitations of conventional oncolytic virotherapy. While traditional live virus delivery systems face substantial challenges including immune-mediated clearance and complex manufacturing workflows, our analysis reveals that encapsulating viral genomes (vGenomes) within surface-functionalized nanoparticles establishes a robust delivery platform. By encapsulating vGenomes within functionalized NPs, this platform achieves tumor-targeted delivery via enhanced permeability and retention (EPR) effects or ligand-mediated active targeting. Intracellular release of vGenomes enables in situ production of viral progeny, inducing immunogenic cell death while evading pre-existing antiviral immunity. Preclinical studies demonstrate that NP-vGenome complexes achieve > 80% tumor regression in murine models and maintain efficacy even in neutralizing antibody-rich environments. This review synthesizes the mechanistic synergy between nanotechnology and oncolytic virotherapy, providing a roadmap for next-generation cancer immunotherapy.