A Comprehensive Review on Copper Oxide Nanoparticles: Physicochemical Parameters, Pharmacological Potential and...

Copper oxide nanoparticles (CuONPs) have attracted considerable attention in biomedical research owing to their unique physicochemical properties, high surface reactivity, and versatile biological activities. Their nanoscale dimensions have enabled diverse applications in antimicrobial therapy, anticancer treatment, biosensing, and drug delivery. However, increasing biomedical and environmental exposure to CuONPs has raised significant concerns regarding their biodistribution, biocompatibility, and potential toxicological effects. Unlike previous reviews that have generally addressed these aspects separately or with limited integration, this review integrates the physicochemical characteristics, exposure routes, biodistribution, pharmacological activities, and toxicological effects of CuONPs to provide a comprehensive understanding of their biomedical potential and safety. Emphasis is placed on the influence of inhalational, oral, dermal, and parenteral exposure routes and biological interactions of CuONPs, including their cellular internalization, protein corona formation, systemic translocation, and organ-specific accumulation. Furthermore, the review comprehensively examines the therapeutic applications of CuONPs, highlighting their antibacterial, anticancer, antidiabetic, and antioxidant properties, while also discussing their associated toxicity such as oxidative stress, inflammatory responses, genotoxicity, and regulated cell death pathways such as apoptosis, autophagy, ferroptosis, and cuproptosis. Evidence from both in vitro and in vivo studies demonstrates that CuONPs can induce significant pulmonary, hepatic, renal, neurological, reproductive, and haematological toxicities depending on their physicochemical properties and exposure conditions. Overall, this review highlights the dual role of CuONPs as both promising nanotherapeutic agents and potential toxicological hazards, emphasizing the need for standardized biological evaluation, safer nanoparticle design strategies, and improved understanding of biodistribution and long-term biological effects to support their future clinical translation.