Enhancing Oncolytic Virus Therapy with Nanomedicine: A Review of Progress, Challenges, and Future Directions in a New Frontier of Cancer Treatment

Oncolytic viruses (OVs) are a new generation of tumor-specific biological agents that can selectively kill cancer cells. They replicate uniquely within tumors, showing significant potential for the advancement of precision cancer therapy. OVs have a dual action: they directly lyse malignant cells through selective viral replication in tumor tissues and activate the host's systemic antitumor immune response, thereby creating a comprehensive immune defense network. However, their clinical efficacy is often limited by rapid systemic clearance, poor tumor tissue penetration, and off-target effects. Nanotechnology has emerged as a transformative strategy to overcome these delivery barriers. This review highlights how intelligent nanocarriers enhance OV therapy through improved pharmacokinetics, active targeting, and controlled release within the tumor microenvironment. We further discuss rational combination strategies with conventional therapies (e.g. chemotherapy, radiotherapy) and immunomodulatory agents to achieve synergistic antitumor efficacy. Finally, we critically examine the current challenges and future translational prospects of nano-engineered OVs, providing a framework for advancing these innovative platforms toward clinical application and the development of next-generation cancer therapeutics.