Lai Xiangdong, Zhang Xiaoyang, Lai Jiejuan, Zhao Weiwei, Song Zhongquan, Chen Yuanyuan, Ud Din Miraj, Munawer Muhammad Faizan, Jiang Hui, Liu Xiaohui, Wang Xuemei
State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China.
Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China.
Mater Today Bio. 2025 Apr 17;32:101774. doi: 10.1016/j.mtbio.2025.101774. eCollection 2025 Jun.
NFκB is a vital transcription factor for the regulation of hair follicle cycle. As a therapeutic target, NFκB is specifically blocked by RNA aptamer with negligible side effects, but the targeted transmembrane transport of anti-NFκB aptamer remains a challenge due to its negative charge under physiological conditions. In this study, taking advantage of the depilation-induced oxidative stress microenvironment (OSM), it was confirmed for the first time that self-assembled gold nanoclusters and aptamer (AuNCs-Aptamer) complexes formed in the skin and enhanced the therapeutic effect of anti-NFκB aptamer drugs, effectively blocking the NFκB-mediated inflammatory response and inhibiting hair follicle regeneration. The hematoxylin-eosin (HE) staining of tissue section and hematology analysis demonstrated that OSM-responsive self-assembled AuNCs-Aptamer caused no toxicity to the living organism. Moreover, self-assembly occurred only in the oxidative stress-injured skin cells rather than the normal cells, which revealed that this self-assembly was a targeted, safe and effective therapy for hypertrichosis.
核因子κB（NFκB）是调节毛囊周期的重要转录因子。作为一种治疗靶点，RNA适配体可特异性阻断NFκB，且副作用可忽略不计，但抗NFκB适配体在生理条件下因其负电荷而进行靶向跨膜转运仍然是一个挑战。在本研究中，利用脱毛诱导的氧化应激微环境（OSM），首次证实自组装金纳米簇与适配体（AuNCs-适配体）复合物在皮肤中形成，并增强了抗NFκB适配体药物的治疗效果，有效阻断了NFκB介导的炎症反应并抑制毛囊再生。组织切片的苏木精-伊红（HE）染色和血液学分析表明，OSM响应性自组装AuNCs-适配体对生物体无毒性。此外，自组装仅发生在氧化应激损伤的皮肤细胞而非正常细胞中，这表明这种自组装是一种针对多毛症的靶向、安全且有效的治疗方法。
