Polysulfonium: Unveiling a Bioactive Polymer to Induce Immunogenic Cell Death for Anticancer Therapy.

ABSTRACT

Here we report a brand-new bioactive polymer featuring sulfonium moieties that exhibits the capability of inducing immunogenic cell death (ICD) for anticancer therapy. The optimized polysulfonium presents a wide spectrum of potent anticancer activity and remarkable selectivity. In-depth mechanistic studies reveal that the polymer exerts its cytotoxic effects on cancer cells through a membrane-disrupting mechanism. This further initiates the release of a plethora of damage-associated molecular patterns, effectively triggering ICD and resulting in systemic anticancer immune responses. Notably, the compound demonstrated significant efficacy in suppressing tumor growth in the B16-F10 melanoma tumor model. Furthermore, it exhibits robust immune memory effects, effectively suppressing tumor recurrence and metastasis in both the rechallenge model and the lung metastatic tumor model. To the best of our knowledge, the study represents the pioneering exportation of cationic polysulfoniums, showcasing not only their remarkable safety and efficacy against primary tumors but also their unique ability in activating long-term immune memory.