Emerging role of copper nanoparticles in the diagnosis and treatment of lung cancer

Structured Abstract Background Lung cancer is the leading cause of cancer-related mortality worldwide, and current therapies are limited by drug resistance, systemic toxicity, and inadequate tumor selectivity. Copper oxide nanoparticles (CuO NPs), derived from an essential trace element, exhibit inherent redox activity and cytotoxicity toward tumor cells, making them a promising candidate for precision lung cancer therapy. However, their clinical advancement remains hindered by safety concerns. Methods This review critically evaluates recent preclinical studies on CuO NPs in lung cancer, with emphasis on how physicochemical features including particle size, zeta potential, morphology, dissolution kinetics, and surface functionalization influence bioactivity and toxicity. Evidence from in vitro cytotoxicity, mechanistic assays, in vivo biodistribution, and safety studies was synthesized to connect nanoparticle design parameters with therapeutic outcomes. Results CuO NPs induce potent anticancer effects through reactive oxygen species (ROS) generation, mitochondrial dysfunction, apoptosis, cell cycle arrest, and emerging cuproptosis pathways. Surface-engineered and ligand-functionalized CuO NPs demonstrate improved tumor selectivity, while inhalable formulations enhance pulmonary delivery. Synergistic effects were observed when combined with chemotherapeutics or immunotherapy, enabling dose reduction. Nonetheless, dose-dependent pulmonary inflammation, oxidative injury, and hepatic and renal accumulation raise significant toxicological concerns. Conclusion CuO NPs offer a versatile nanoplatform for lung cancer theranostics, bridging trace element biology with targeted nanomedicine. However, unresolved challenges including toxicity, biodistribution control, and regulatory barriers require optimized nanoparticle engineering, safer synthesis methods, and rigorous risk assessment to enable clinical translation.