Biomimetic polydopamine loaded with janus kinase inhibitor for synergistic vitiligo therapy via hydrogel microneedles

作者：Chunying Li, Wenwen Wang, Junyi Shao, Sen Zhou, Xiaolin Ji, Youxia Xi, Qiuyang Xu, Yuhan Huang, Jingle Wang, Yilin Wan, Zhiming Li · 发表于：Journal of Nanobiotechnology · 年份：2025 · DOI：10.1186/s12951-025-03119-1 · 被引用次数：19 · 研究领域：melanin and skin pigmentation、Advancements in Transdermal Drug Delivery、Neurobiology and Insect Physiology Research

Both oxidative stress and autoimmune responses play crucial roles in the development of vitiligo. Under oxidative stress, the apoptotic melanocytes expose self-antigens and release high mobility group box 1 (HMGB1), triggering autoimmune activation and recruiting CD8 + T cells. This process further leads to the destruction of melanocytes, resulting in the lack of melanin granules. Additionally, the accumulated CD8 + T cells release interferon-γ (IFN-γ) to activate janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway in keratinocytes. Both oxidative stress and IFN-γ-JAK-STAT activation induce keratinocytes to express and release T cell chemotactic factors, exacerbating the process of vitiligo. Reducing the accumulation of CD8 + T cells by safeguarding melanocytes and keratinocytes from oxidative stress may be contemplated as a promising approach for vitiligo therapy. In this study, we introduce a novel therapeutic agent called PDA-JAKi, which is capable of both eliminating oxidative stress and inhibiting T cell activation. Specifically, we have incorporated the janus kinase inhibitor (JAKi) tofacitinib into antioxidant polydopamine (PDA) nanoparticles, resulting in the formation of uniform PDA-JAKi nanodrug. PDA-JAKi effectively mitigates oxidative stress-induced apoptosis in melanocytes, reducing the antigen presentation and release of HMGB1. In addition, PDA-JAKi simultaneously attenuates oxidative stress and blocks the IFN-γ-JAK-STAT pathway to r...