An Ion-Enhanced Oncolytic Virus-Like Nanoparticle for Tumor Immunotherapy

T lymphocytes (T cells) are essential for tumor immunotherapy. However, the insufficient number of activated T cells greatly limits the efficacy of tumor immunotherapy. Herein, we proposed an oncolytic virus-mimicking strategy to enhance T cell recruitment and activation for tumor treatment. We constructed an oncolytic virus-like nanoplatform (PolyIC@ZIF-8) that was degraded in the acidic tumor environment to release PolyIC and Zn²⁺ . The released PolyIC exhibited an oncolytic virus-like function that induced tumor cell apoptosis and promoted T cell recruitment and activation through a tumor antigen-dependent manner. More importantly, the released Zn²⁺ not only enhanced T cell recruitment by inducing CXCL9/10/11 expression but also promoted T cell activation to increase interferon-γ (INF-γ) expression by inducing the phosphorylation of ZAP-70 via a tumor antigen-independent manner. This Zn²⁺ -enhanced oncolytic virus-mimicking strategy provides a new approach for tumor immunotherapy.