Cu²⁺-Citrate-Chitosan Complex Nanoparticles for the Chemodynamic Therapy of Lung Cancer

Lung cancer poses a significant threat to human health. Surgical intervention is the preferred treatment modality for lung cancer, but a large number of patients are deprived of the opportunity for surgery for various reasons and are compelled to undergo radiotherapy and chemotherapy, which entail systemic adverse reactions. In recent years, with the advancement of nanomedicine, chemodynamic therapy (CDT) based on free radicals has been extensively investigated. In this study, we fabricated copper-citrate-chitosan composite nanoparticles (CuCC NPs) by encapsulating copper-citrate complexes with natural chitosan polymers, resulting in a substantial reduction in the biotoxicity of copper ions. The CuCC NPs selectively accumulated in tumor tissues through the enhanced permeability and retention effect (EPR) and gradually degraded within the acidic and glutathione (GSH)-rich microenvironment of the tumor, thereby releasing the loaded copper ions. Through CDT, the copper ions converted the overexpressed hydrogen peroxide (H₂O₂) in the tumor tissue into hydroxyl radicals (•OH), leading to the eradication of tumor cells. In animal experiments, CuCC NPs exhibited remarkable efficacy in CDT. Further histopathological and hematological analyses demonstrated that CuCC NPs could induce substantial apoptosis in tumor tissues while maintaining an extremely high level of safety.