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 high-mobility group box 1 (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.