Membrane-disrupting saponin-polyphenols as tumor nanovaccine via immunogenic cell death and antigen capture

Converting localized tumor destruction into systemic antitumor immunity remains a central challenge in cancer immunotherapy. In this study, we present a rationally designed antigen-capturing nanoplatform composed of tannic acid (TA) and saponin, which self-assemble to encapsulate photosensitizer, forming saponin-polyphenol nanoparticles (ISNPs) with multifunctional immunotherapeutic potential. Leveraging the membrane-perturbing properties of saponin, ISNPs induce acute plasma membrane disruption and promote the release of damage-associated molecular patterns (DAMPs), such as calreticulin (CRT) and HMGB1, thereby initiating immunogenic cell death (ICD) and supporting subsequent immune activation. Simultaneously, ISNPs induce nuclear membrane rupture and cytosolic DNA leakage. Notably, the polyphenol-rich surface of ISNPs enables efficient adsorption of tumor-associated antigens (TAAs), forming antigen–nanocomplexes that prolong antigen retention and facilitate dendritic cell (DC) uptake. In bilateral tumor-bearing mouse models, ISNP-mediated photothermal treatment not only eradicates primary tumors but also elicits a modest abscopal trend on distant lesions, marked by enhanced DC maturation and cytotoxic T lymphocyte infiltration. This work establishes a membrane-interfering, antigen-capturing nanoagent that effectively bridges local photothermal ablation and systemic immune activation, offering a promising strategy for in situ nanovaccination and personalized cancer immunotherapy.