Journal of nanobiotechnology · 2026
Microneedle-mediated transdermal delivery of siRNA-loaded nanoparticles for atopic dermatitis therapy by disrupting cuproptosis-pyroptosis crosstalk.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Yu Pian, Fang Chi, Luo Zhisheng, Hao Lu, Li Kaixuan, Yan Rongxuan, Ma Sihui, Wang Guanming, Cao Qiaozhi, Dong Jie, Chen Xiang, Li Jie, Liu Peng, Hu Shuo, Peng Cong
Аннотация
BACKGROUND: Atopic dermatitis (AD) is a common chronic inflammatory skin disorder characterized by epidermal barrier dysfunction and immune dysregulation, yet effective long-term therapies are limited. Although regulated cell death has been linked to AD, the involvement of copper-dependent cell death (cuproptosis) and its therapeutic relevance in AD have not been explored.
RESULTS: Herein, we identify aberrant epidermal upregulation of the copper transporter SLC31A1 as a driver of copper overload and cuproptosis in keratinocytes, which in turn promotes GSDMA-dependent pyroptosis through an α-ketoglutarate (α-KG)/H3K9me3 epigenetic mechanism. To target this pathway, we developed a dual-functional microneedle system composed of calcium phosphate nanoparticles delivering Slc31a1 siRNA and embedded within Bletilla striata polysaccharide microneedles (CaP-siSlc31a1@BSP). This platform enables efficient transdermal gene silencing while BSP simultaneously suppresses STAT3/GSDMA signaling and inflammation. In MC903-induced AD-like mice, CaP-siSlc31a1@BSP markedly alleviated skin inflammation, epidermal hyperplasia and pruritus, accompanied by reduced Th2/Th17 responses.
CONCLUSIONS: Our study reveals a previously unrecognized cuproptosis-pyroptosis axis in AD and establishes SLC31A1 as a promising therapeutic target. The CaP-siSlc31a1@BSP microneedle offers a synergistic drug-gene transdermal strategy with strong potential for AD treatment.
RESULTS: Herein, we identify aberrant epidermal upregulation of the copper transporter SLC31A1 as a driver of copper overload and cuproptosis in keratinocytes, which in turn promotes GSDMA-dependent pyroptosis through an α-ketoglutarate (α-KG)/H3K9me3 epigenetic mechanism. To target this pathway, we developed a dual-functional microneedle system composed of calcium phosphate nanoparticles delivering Slc31a1 siRNA and embedded within Bletilla striata polysaccharide microneedles (CaP-siSlc31a1@BSP). This platform enables efficient transdermal gene silencing while BSP simultaneously suppresses STAT3/GSDMA signaling and inflammation. In MC903-induced AD-like mice, CaP-siSlc31a1@BSP markedly alleviated skin inflammation, epidermal hyperplasia and pruritus, accompanied by reduced Th2/Th17 responses.
CONCLUSIONS: Our study reveals a previously unrecognized cuproptosis-pyroptosis axis in AD and establishes SLC31A1 as a promising therapeutic target. The CaP-siSlc31a1@BSP microneedle offers a synergistic drug-gene transdermal strategy with strong potential for AD treatment.