NIR-II laser-mediated photo-Fenton-like reaction via plasmonic Cu9S8 for immunotherapy enhancement

Chemodynamic therapy (CDT) is typically used to modulate the immunogenic tumor microenvironment and extend the benefits of immune checkpoint therapy because of its good tumor selectivity. However, the poor catalytic efficiency of CDT agents means that it often needs to be combined with other enhancement strategies, such as radiotherapy and photothermal therapy with high power density, which can inevitably traumatize normal tissues. To overcome these limitations, a near-infrared (NIR)-II laser-mediated photo-Fenton-like reaction based on a plasmonic self-doped semiconductor was proposed as a mild enhancement strategy to enhance the immune responses. Experimental simulations and results of plasmonic Cu9S8 show that the NIR-II laser can enhance the CDT effect based on the plasmon-driven photoredox chemistry without inducing a photothermal effect. Furthermore, the enhanced CDT effectively induces immunogenic cell death and dendritic cell maturation both in vitro and in vivo. In addition, the antitumor immune response is greatly enhanced by the synergistic effect of the NIR-II laser in enhancing both CDT and anti-PD-L1. This allows for primary tumor elimination and the effective suppression of distant tumors and lung metastases. Our proposed design indicates that the NIR-II photo-Fenton-like reaction based on the plasmonic semiconductor effectively enhances CDT, thus selectively enhancing immunotherapy.