A targeted therapy for salivary adenoid cystic carcinoma: A homologous bimetal nanoplatform via the cGAS-STING-mediated immunostimulation

Due to its high heterogeneity and immunosuppressive nature, salivary adenoid cystic carcinoma (SACC) has posed serious challenges for the prognostic outcomes of the afflicted patients. In this study, we designed a degradable bimetallic composite nanoparticle (MFMIMON) with a homologous targeting property against SACC, which systemically conferred the antitumor immunity in this prototypical “cold” tumor and integrated diagnosis and therapy via a synergistic magnetic resonance imaging/near-infrared (NIR) fluorescence multimodal imaging. Upon 808 nm laser irradiation, the nanoparticles leveraged their multiple enzyme-mimicking activities to promote the generation of intracellular reactive oxygen species, deplete glutathione, and exacerbate the oxidative stress through the photodynamic therapy (PDT), photothermal therapy (PTT), or chemodynamic therapy (CDT), while simultaneously generating oxygen to sustain the efficacy of PDT or CDT. This cascade effectively induced the immunogenic cell death in tumor cells, markedly enhanced the adaptive antitumor immune responses and the infiltration of cytotoxic T lymphocytes, and ultimately suppressed the growth of both primary and metastatic tumors. These findings highlight the proposed NIR-triggered spatiotemporal regulatory platform as an effective therapeutic paradigm for reversing the “cold” nature of SACC and limiting its systemic metastasis.