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

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.