Biointerface-Engineered Gold and Silver Nanoparticles for Skin Cancer Therapy: Linking Nano-Biointerface Design to Therapeutic Function and Clinical Translation.

Skin cancer therapy continues to face challenges in achieving selective tumour targeting while limiting damage to healthy tissue. Gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) have emerged as versatile platforms for skin cancer treatment, but their therapeutic behaviour is strongly influenced by the nano-biointerface. This review critically examines how particle size, morphology, surface chemistry, ligand functionalization, and biomimetic coatings influence skin penetration, cellular uptake, tumour localization, and therapeutic activity. The reviewed evidence indicates that AuNPs are particularly suited to photothermal and photodynamic therapies because their plasmonic properties enable localized light-mediated effects, whereas AgNPs exhibit prominent cytotoxic activity associated with reactive oxygen species generation and modulation of the tumour microenvironment. Biointerface engineering can further enable active targeting, improve colloidal stability, alter biodistribution, and integrate multiple therapeutic functions. However, reported improvements in therapeutic efficacy are accompanied by unresolved concerns regarding nanoparticle stability, reproducibility, long-term toxicity, biodistribution, and standardization. Overall, the evidence indicates that nanoparticle performance cannot be considered independently of the nano-biointerface. Rational control of interfacial properties is therefore central to improving targeting precision and therapeutic performance, while standardized characterization, mechanistic understanding, and systematic safety evaluation remain essential for clinical translation.