Hair turning white is a multifactorial pigment disorder caused by dysfunction of melanocytes. Due to the deep localization of follicular melanocytes and the limited efficiency of current bioactive macromolecule transdermal delivery systems, effective treatment is challenging. This article introduces a rational-designed transdermal therapy that uses polymeric tyrosinase nanocapsules (nTIR) to directly activate local melanocytes and stimulate melanin production in situ. Under the guidance of the penetration model established in our research, the size and surface potential of nTYRs were optimized to enhance skin permeability and maintain enzyme activity. nTYRs efficiently deliver active tyrosinase through the stratum corneum to hair follicle melanocytes, achieving rapid and robust hair pigmentation restoration. The efficacy and safety of nTYRs have been verified in mouse and human melanocyte models as well as pig and human skin models. An immune-mediated endogenous alopecia mouse model was developed to approximate human pathophysiology and directly evaluate the effect of nTYR on damaged melanocytes. This study provides a promising and widely applicable strategy for reversing hair loss, with direct efficacy, minimal side effects, and potential for synergy with existing therapies. This research was published in ACS Nano under the title "Direct Activation of Follicular Melanocytes by Polymeric Tyrosinase Nanocapsules for Reversing Hair Graying".
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DOI: 10.1021/acsnano.5c2178