Ceria-Based Nanotherapeutics for Inflammatory Skin Disorders: From Design and Mechanisms to Advanced Delivery and...

Inflammatory skin diseases, including atopic dermatitis (AD), psoriasis, diabetic wounds, and photoaging, represent major public health challenges due to their high prevalence, chronic recurrence, and substantial disease burden. Current treatments, such as glucocorticoids, calcineurin inhibitors, and biologics, are often constrained by limited efficacy, long-term adverse effects, or high costs, highlighting the need for safer and more accessible therapeutic strategies. Cerium oxide nanoparticles (CeO₂ NPs) have attracted increasing attention because of their reversible Ce³⁺/Ce⁴⁺ redox cycling and multiple enzyme-mimetic activities. This review examines the synthesis strategies and structure-activity relationships of CeO₂ NPs, and discusses their antioxidant, anti-inflammatory, immunomodulatory, antimicrobial, and proangiogenic mechanisms in inflammatory skin microenvironments. We further evaluate their applications in AD, psoriasis, diabetic wounds, and photoaging, and summarize advanced delivery approaches involving structural functionalization, biomimetic surface modification, and formulation hybridization. Key translational challenges, including long-term safety, degradability, manufacturing consistency, and disease-specific applicability, are also discussed. Finally, we propose a "5D" framework for next-generation CeO₂-based nanomedicines, integrating disease-specific design, degradability, data-driven optimization, device integration, and digital health interfacing.