Gold and Silver Nanoparticles in Biomedical Applications: Cytotoxicity, Mechanism of Action, and Future Challenges

Abstract: Gold (Au) and silver (Ag) nanoparticles have gained significant attention in biomedicine due to their unique physicochemical and biological properties. This review critically examines their synthesis approaches, characterization techniques, cellular uptake mechanisms, cytotoxic profiles, and biomedical applications, with emphasis on safety considerations. AuNPs are distinguished by their chemical stability, tunable surface chemistry, and excellent biocompatibility, which support applications in drug delivery, imaging, and photothermal therapy. In contrast, AgNPs exhibit strong antimicrobial activity, mainly through oxidative stress and membrane disruption, though cytotoxicity varies considerably with particle size, charge, and surface modification. Smaller nanoparticles (<20 nm) are more prone to inducing ROS and DNA damage, while strategies such as PEGylation, ligand conjugation, and encapsulation reduce toxicity and improve therapeutic precision. Emerging directions include hybrid Au–Ag core–shell systems and greensynthesized nanoparticles, which show promise for enhanced safety and efficacy. By harmonizing synthesis design with biological responses, researchers can improve the translational potential of these nanomaterials, ensuring both clinical safety and therapeutic effectiveness.