ArticleInternational journal of nanomedicine2026
Stimulator of Interferon Genes (STING) Agonist-Loaded Copper-Based Nanoparticles for B7-H3 Blockade-Enhanced Chemodynamic-Immunotherapy of Ovarian Cancer.
Article in International journal of nanomedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: Ovarian cancer remains difficult to treat because of limited tumor immunogenicity, poor cytotoxic T-cell infiltration, and a strongly immunosuppressive tumor microenvironment. Methods: Characterization, in vitro cell experiments, and tumor mouse model was performed. Results: Here, we developed an anti-B7-H3 antibody-modified, STING agonist-loaded copper-based nanoplatform for tumor-targeted chemodynamic-immunotherapy. The copper-containing nanoparticles enabled efficient loading of the non-nucleotide STING agonist MSA-2 and exhibited acid-responsive release of both MSA-2 and copper ions. Reactive oxygen species generation and intracellular glutathione depletion amplify oxidative stress, induce tumor-selective cytotoxicity, and trigger immunogenic cell death, as evidenced by increased release of ATP and HMGB1. Surface conjugation with anti-B7-H3 antibody preserved B7-H3-blocking activity and enhanced nanoparticle uptake, intracellular copper delivery, tumor accumulation in ovarian cancer cells. In vivo, the nanoplatform produced the strongest tumor-growth inhibition and significantly prolonged survival compared with non-targeted or single-component formulations. MSA-2 delivery was associated with enhanced STING pathway activation, increased inflammatory cytokine production, and improved antitumor immune responses, while anti-B7-H3 antibody modification promoted tumor accumulation. Importantly, the nanoplatform showed favorable biocompatibility, with no evident body-weight loss, major-organ injury, hematological abnormalities, or hepatic and renal dysfunction. Conclusion: This multifunctional nanoplatform integrates B7-H3-mediated tumor targeting and immune blockade, copper-based chemodynamic therapy, immunogenic cell death, and STING activation, providing a promising strategy for remodeling the ovarian tumor immune microenvironment and enhancing systemic antitumor immunity.
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