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

Jin Qiu,1,2,* YongMei Liao,1,* Daohong Kan,3,* Li Liao,4,* Kaiwen Yang,2 Xiaoran Hu,5 Zhongming Wang,6 Hongru Yu,7 Fang Xie,8 Zongjunlin Liu1 1Department of Dermatology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 3Department of Burn and Plastic Surgery, The Second People’s Hospital of Yibin, Yibin, Sichuan, People’s Republic of China; 4Department of Pharmaceutical, The Second People’s Hospital of Yibin, Yibin, Sichuan, People’s Republic of China; 5Department of Pain, Luzhou People’s Hospital, Luzhou, Sichuan, People’s Republic of China; 6Department of Internal Medicine, Gongxian Hospital of Traditional Chinese Medicine, Yibin, Sichuan, People’s Republic of China; 7Department of Orthopaedics and Traumatology, Gongxian Hospital of Traditional Chinese Medicine, Yibin, Sichuan, People’s Republic of China; 8Department of Oncology, The Second People’s Hospital of Yibin, Yibin, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zongjunlin Liu, Email [email protected] Fang Xie, Email [email protected]: 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. Keywords: oncolytic virus, nanomedicine, anti-tumor, targeting delivery, immune activation