Hyaluronic acid-modified mesoporous manganese dioxide combined with carboplatin synergistically enhances ovarian cancer therapy

: Ovarian cancer (OC) remains a highly lethal malignancy with substantial clinical challenges, including severe side effects and acquired resistance associated with conventional chemotherapeutics such as carboplatin (CBP). To address these limitations, we developed a dual-therapy nanoplatform by co-loading CBP and hyaluronic acid (HA) onto hyaluronic acid-functionalized manganese-based nanoparticles via a facile incubation method. The resulting CBP@HMnO 2 @HA nanoparticles exhibited a uniform hydrodynamic diameter of 210.3 nm and a zeta potential of −31.2 mV, enabling effective tumor-targeted delivery for combined chemotherapy and chemodynamic therapy. In vitro studies demonstrated that the nanoparticles markedly enhanced reactive oxygen species (ROS) generation via peroxidase-like activity and triggered immunogenic cell death (ICD), as evidenced by the pronounced release of damage-associated molecular patterns (DAMPs) including ATP and HMGB1. In vivo biodistribution studies showed significant tumor-specific accumulation within 24 h post-injection, leading to potent suppression of tumor growth. Mechanistically, the antitumor efficacy was associated with activation of the cGAS-STING signaling pathway. Collectively, these results indicate that CBP@HMnO 2 @HA nanoparticles possess integrated chemotherapeutic, chemodynamic, and robust catalytic functionalities, offering a promising multimodal nanotherapeutic strategy for the treatment of ovarian cancer.