Therapeutic potential of metallic nanocarriers in the treatment of psoriasis: current advances, mechanistic insights, and translational perspectives

Psoriasis is a chronic, immune-mediated inflammatory skin disorder characterized by dysregulated keratinocyte proliferation, aberrant immune activation, and impaired skin barrier function. Despite the availability of conventional topical, systemic, and biologic therapies, their long-term efficacy is often limited by poor skin penetration, systemic side effects, high cost, and patient non-compliance. In this context, metallic nanoparticles (MNPs) have emerged as a transformative nanotechnological platform for topical psoriasis management, owing to their unique physicochemical properties, including high surface area, tunable size, surface functionalization, and intrinsic bioactivity. This review comprehensively explores next-generation metallic nanocarrier-based topical systems, focusing on their role in overcoming skin barrier limitations and enabling targeted, controlled drug delivery. Particular emphasis is placed on mechanistic insights into how MNPs modulate key pathogenic pathways, including NF-κB, MAPK, JAK/STAT, and IL-23/Th17 axes, thereby exerting anti-inflammatory, antioxidant, and immunomodulatory effects. Various classes of metallic nanoparticles, including gold, silver, zinc oxide, cerium oxide, and hybrid metal-based systems, are critically evaluated in terms of their therapeutic efficacy, formulation strategies, and translational potential. Furthermore, this review highlights key challenges such as toxicity, bioaccumulation, scalability, and regulatory constraints that currently hinder clinical translation. Finally, emerging advancements in stimuli-responsive systems, green synthesis approaches, and nanotheranostics are discussed as promising directions for future research. Collectively, metallic nanocarriers represent a multifunctional and highly promising platform with the potential to redefine precision topical therapy for psoriasis. Clinical trial number: NA.