Supramolecular Polypeptide Self-Assembly Mediated In Situ Elicitation of Robust Innate and Adaptive Immune Responses Boosts Immunogenic Photothermal Therapy toward “Cold” Tumor



As a promising cancer treatment modality that has  emerged, photothermal therapy can harness antitumor immunity by  triggering immunogenic cell death (ICD) in addition to direct cell  ablation. However, the immuno-stimulation induced by PTT alone is  insufficient to achieve satisfactory cancer eradication, especially in  immunologically “cold” tumors due to their harsh immunosuppressive  microenvironment. Effective activation of the innate immune system is  indispensable to boost a robust adaptive antitumor immune response  typically initiated by dendritic cells (DCs). Herein the above issues  are addressed by constructing an environmentally responsive  supramolecular nanoself-assembly (PSAs) derived from a novel  polypeptide-based block copolymer, which is capable of co-load  photothermal immunomodulators efficiently under structure-guided π–π  stacking interactions. In the murine model of 4T1 xenograft tumors, the  fabricated PSAs with payloads trigger both adaptive and innate immune  responses in situ through activation of ICD as well as STING-dependent  signal pathway. The findings reveal a new mechanism of harnessing  photothermal therapy toward immunologically “cold” tumors.