Nitrogen-Boosted H2O2 Production of Arginine-Polyphenol Nanozyme Drives Oxidative Eustress for Hair Regeneration

November 2025 in “ Advanced Science ”

Yifei Wang, Yaojia Yang, Aoxue Wang, Chen Shen, Shenliang Tan, Changsheng Liu, Yuzheng Zhao, Xue Qu

polyphenol–amino acid nanozyme H2O2 oxidative eustress hair regeneration epigallocatechin gallate L-arginine telogen effluvium Wnt/β-catenin Ca2+/calcineurin/NFAT alopecia EGCG L-Arg

Studysummary In this study, researchers developed a polyphenol–amino acid nanozyme capable of controlled hydrogen peroxide delivery, which effectively activated hair follicles via oxidative stress in a mouse model, suggesting a potential non-pharmacological treatment for alopecia.

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The study presents a novel approach to hair regeneration using nitrogen-boosted arginine-polyphenol nanozymes (PEAs) that produce controlled hydrogen peroxide (H2O2) levels to drive oxidative eustress. These nanozymes, particularly PEA-4, enhance hair follicle stem cell activation by upregulating the Wnt/β-catenin pathway and downregulating the Ca2+/calcineurin/NFAT pathway, promoting the transition from the telogen to anagen phase. In a telogen effluvium mouse model, PEA-4 delivered via hyaluronic acid microneedles significantly improved hair regrowth, surpassing minoxidil, by increasing hair-shaft diameter, pigmentation, and coverage area. The study suggests that these nanozymes could be effective in hair regeneration therapies by modulating oxidative stress in a controlled manner.

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