A Biodegradable 2D Metallic MoS₂ Genesheet for Synergistic NIR‐II Photothermal Immunotherapy

Abstract Developing promising biodegradable second near‐infrared (NIR‐II) immune agonists to overcome the insufficient immunogenicity of tumor cells and the poor immune response remains challenging. In this work, a biodegradable “2D genesheet” is explored for synergistic NIR‐II photothermal immunotherapy. The 2D genesheet is large‐scale prepared through flexible supramolecular self‐assembly between metallic‐MoS₂ and siRNA. The 2D genesheet not only exhibits an excellent photothermal conversion efficiency up to 56% in the NIR‐II window, but also features unique H₂O₂‐responsive biodegradability and high biocompatibility. The 2D genesheet can efficiently deliver siRNA(siIDO) to tumor cells and downregulate indoleamine 2,3‐dioxygenase 1 (IDO1) protein expression, exerting intrinsic immune activation and reversing IDO1‐mediated immunosuppression. The spatiotemporal‐controlled NIR‐II phototherapy can elicit systemic immunity by evoking immunogenic cell death, promoting dendritic cell maturation, and increasing T cell infiltration. The bioactive material is able to efficiently inhibit primary and distant tumors, achieving a 100% tumor eradication rate. This study broadens the application prospects of biodegradable NIR‐II immune agonists, overcoming the limitations of current immunotherapeutic modalities.