Recently,
photothermal therapy (PTT) in the second near-infrared (NIR-II) biowindow has emerged as a promising treatment modality; however, its therapeutic outcomes are still limited by heterogeneous heat distribution and insufficient control of metastatic lesions. Tremendous efforts have been made to overcome the PTT's shortcomings by combining PTT with
immunotherapy, but unfortunately current strategies still suffer from low response rates, primary/acquired resistance or severe immune-related adverse events. Herein, a novel photothermal agent and gene co-delivery nanoparticle (CSP), with
CuS inside the SiO2 pore channels and
PDMAEMA polycation on the outside of SiO2 surface, is explored for
tumor localized NIR-II PTT and in situ
immunotherapy through local generation of
IL-12 cytokine. The resulting CSP integrated with the plasmid encoding
IL-12 gene (CSP@
IL-12) exhibited good gene transfection efficiency, outstanding NIR-II PTT effect and excellent therapeutic outcomes both in vitro and in vivo. Meanwhile, such an in situ joint
therapy modality could significantly induce systemic immune responses including promoting DC maturation, CD8+ T cell proliferation and infiltration to efficiently eliminate possible metastatic lesions through abscopal effects. Hence, this creative combinational strategy of NIR-II PTT and
IL-12 cytokine therapy might provide a more efficient, controllable and safer alternative strategy for future photo-
immunotherapy.