Innovative Biomaterials Synergize Oncolytic Virus for Elevating Tumor Immunotherapy Potency

Cancer immunotherapy, particularly using oncolytic viruses (OVs), has been recognized as a promising approach for treating malignant tumors because of its dual ability to selectively kill tumor cells and activate antitumor immunity. However, OV monotherapy faces inherent challenges, including suboptimal viral delivery efficiency, an immunosuppressive tumor microenvironment, and premature systemic-immune clearance. Recent breakthroughs in biomaterials have provided new avenues for optimizing oncolytic virotherapy by overcoming these limitations using innovative system designs. In this review, we systematically examined the synergistic combination of biomaterials with OVs to enhance cancer immunotherapy, emphasizing two major categories: nanomaterial-based carriers and cell-derived materials. Intelligent biomaterial delivery systems can spatiotemporally protect viruses from immune clearance and enable targeted accumulation and controlled release. Functionalized biomaterials can serve as immunomodulators or drug carriers that synergize with OVs to remodel the tumor microenvironment. Particular focus was placed on biomimetic virus-like nanoparticles, and their design principles, mechanisms, and applications were critically discussed in this review. Finally, we summarize the potential challenges and prospects of combining biomaterials with OVs to enhance cancer immunotherapy, paving the way for a clinical translation of this approach.