Abstract

Head and Neck Squamous Cell Carcinoma (HNSCC), characterized by a propensity for recurrence and metastasis, underscores the inadequacies of existing treatments. In this research, a liposome called DI@Lipo was developed to co-deliver cisplatin (DDP) and indocyanine green (ICG), aiming to trigger synergistic pyroptosis to enhance antitumor immunity. DI@Lipo cleverly harnessed the light-activated powers of ICG, combined them with DDP’s tumor-killing ability, to induce activation of the NLRP3 inflammasome. This, in turn, spurred gasdermin D into action, setting off a fiery pyroptosis. This chain reaction triggered a substantial release of Damage-Associated Molecular Patterns (DAMPs) and inflammatory cytokines, which in turn stimulated dendritic cells to mature and attracted an influx of killer T cells. In murine models of HNSCC, this combination therapy not only effectively eliminated primary tumors but also induced a potent abscopal effect, suppressing untreated distant tumors. Importantly, this treatment improved overall survival rates without causing notable systemic toxicity. Additionally, the DI@Lipo platform facilitated fluorescence and photoacoustic imaging (PAI) for potential treatment monitoring. These findings highlight how DI@Lipo-triggered pyroptosis could effectively transform immunologically dormant tumors into responsive ones, presenting a practical therapeutic avenue to combat treatment resistance in head and neck squamous cell carcinoma.