Reactive oxygen species in skin diseases: pathogenic mechanisms and nanomaterial-based therapeutic strategies

Reactive oxygen species (ROS) are inevitable by-products of aerobic metabolism and play a dual role in skin physiology and pathology. At physiological levels, ROS act as essential second messengers regulating cellular signaling and maintaining skin homeostasis. However, excessive ROS accumulation disrupts redox balance, leading to oxidative stress, inflammation, barrier dysfunction, and macromolecular damage, which are closely associated with the pathogenesis of various skin diseases, including psoriasis, atopic dermatitis, pigmentary disorders, photoaging, and skin cancers. In recent years, increasing attention has been directed toward nanomaterial-based strategies for precise ROS regulation, owing to their unique physicochemical properties, such as high surface area, tunable antioxidant activity, and enhanced skin permeability. Compared with conventional antioxidants, nanomaterials, including nanozymes, metal-based nanoparticles, biomacromolecular nanomaterials, and ROS-responsive nanocarriers, exhibit superior stability, targeted delivery capability, and sustained therapeutic efficacy. These nanoplatforms can not only efficiently scavenge excessive ROS but also modulate redox-sensitive signaling pathways, inflammatory responses, and skin barrier repair in a disease-specific manner. This review systematically summarizes the core mechanisms by which ROS contribute to the development of skin diseases, with an emphasis on oxidative stress mediated inflammation, macromolecular damage, and barrier impairment. Furthermore, we comprehensively discuss recent advances in nanomaterial-based therapeutic approaches for ROS regulation, highlighting self-therapeutic nanozymes, biomacromolecular antioxidant materials, and antioxidant-loaded nanodelivery systems. Finally, current challenges and future perspectives for the clinical translation of ROS-targeted nanotherapies in dermatology are discussed, aiming to provide a theoretical basis for the rational design of next-generation nanomedicines for skin disease treatment.