Binary pyroptosis-amplified self-assembling prodrug nanomedicine enhances immunogenicity and inhibits abdominal metastasis in ovarian cancer

Ovarian cancer remains a formidable therapeutic challenge due to its high propensity for abdominal metastasis, recurrence, and the presence of an immunosuppressive tumor microenvironment. To overcome these obstacles, we developed a self-assembled nanoplatforms (OSN) by integrating a near-infrared semiconducting polymer with an oxaliplatin(IV) prodrug. This multifunctional design enables a synergistic triple-modality therapy—photothermal therapy (PTT), photodynamic therapy (PDT), and chemotherapy—within a single nanoparticle, effectively enhancing immunogenic cell death (ICD) and systemic antitumor immunity. Upon laser irradiation, OSN generates localized hyperthermia and reactive oxygen species. These effects synergistically enhance oxaliplatin activation and tumor penetration while triggering pyroptosis through dual caspase-1-mediated and caspase-3-dependent pathways. This robust pyroptotic response amplifies the release of damage-associated molecular patterns ( e.g. , ATP, HMGB1) and pro-inflammatory cytokines ( e.g. , IL-18, IL-1 β ), thereby remodeling the immunosuppressive microenvironment, promoting dendritic cell maturation, and facilitating cytotoxic T-cell infiltration. In murine ovarian cancer models, OSN achieved over 90% tumor suppression, significantly outperforming monotherapies. Notably, this nanoplatform establishes long-term immune memory, effectively reducing the risk of tumor relapse. By concurrently targeting immunogenic barriers and metastatic progression through multimodal mechanisms, OSN represents a paradigm-shifting strategy with high clinical translatability for the treatment of aggressive ovarian malignancies. Semiconducting polymer-coupled oxaliplatin nanoprodrug enables photothermal-photodynamic-chem therapy to activate dual pyroptosis pathways for enhanced immunogenicity and suppression of ovarian cancer abdominal metastasis.