Hyaluronic Acid-Modified Mesoporous Manganese Dioxide Combined with Carboplatin Synergistically Enhances Ovarian Cancer Therapy

Abstract

Ovarian cancer (OC) is a prevalent malignant tumor that poses a significant threat to womens health. Conventional chemotherapeutic agents, such as carboplatin, are associated with several limitations, including notable side effects and the emergence of drug resistance. Carboplatin (CBP) and hyaluronic acid (HA) were subsequently loaded into nanoparticles through incubation to construct targeted nanoparticles (210.3 nm, -31.2 mV) capable of delivering both chemotherapy and chemodynamic therapy. In vitro experiments demonstrated that these nanoparticles enhanced ROS generation through enzyme-like activity and induced immunogenic cell death (ICD) by releasing damage-associated molecular patterns (DAMPs), such as ATP and HMGB1. In vivo animal studies revealed that the nanoparticles predominantly accumulated at the tumor site within 24 hours and significantly suppressed tumor growth by activating the cGAS-STING pathway. These findings indicate that the CBP@HMnO2@HA nanoparticles exhibit potent chemotherapeutic and chemodynamic properties, along with strong catalytic activity. This study presents a promising nanotechnology-based strategy for cancer therapy. HighlightsO_LIThe CBP@HMnO2@HA nanoparticles integrate chemotherapy with chemodynamic therapy, thereby enhancing anti-tumor efficacy. C_LIO_LIThese nanoparticles induce ROS-mediated immunogenic cell death, leading to the release of DAMPs, including ATP and HMGB1. C_LIO_LIThrough HA-mediated targeting, the nanoparticles demonstrate preferential accumulation within tumor tissues, resulting in significant tumor growth inhibition in vivo while reducing off-target toxicity. C_LI