Polysulfonium:\nUnveiling a Bioactive Polymer to Induce\nImmunogenic Cell Death for Anticancer Therapy

Here we report a brand-new bioactive polymer featuring\nsulfonium\nmoieties that exhibits the capability of inducing immunogenic cell\ndeath (ICD) for anticancer therapy. The optimized polysulfonium presents\na wide spectrum of potent anticancer activity and remarkable selectivity.\nIn-depth mechanistic studies reveal that the polymer exerts its cytotoxic\neffects on cancer cells through a membrane-disrupting mechanism. This\nfurther initiates the release of a plethora of damage-associated molecular\npatterns, effectively triggering ICD and resulting in systemic anticancer\nimmune responses. Notably, the compound demonstrated significant efficacy\nin suppressing tumor growth in the B16-F10 melanoma tumor model. Furthermore,\nit exhibits robust immune memory effects, effectively suppressing\ntumor recurrence and metastasis in both the rechallenge model and\nthe lung metastatic tumor model. To the best of our knowledge, the\nstudy represents the pioneering exportation of cationic polysulfoniums,\nshowcasing not only their remarkable safety and efficacy against primary\ntumors but also their unique ability in activating long-term immune\nmemory.