Hu Xingjie, Guo Lihao, Ding Yinghao, Nie Shiyu, Fang Jingqi, Li Jie, Han Quanhong, Ding Dan, Zhang Qian, Wang Tingliang, Wang Ling, Wang Mandi, Yang Zhimou
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin, 300071, PR China.
Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325035, Zhejiang Province, PR China.
Bioact Mater. 2025 Aug 6;53:819-830. doi: 10.1016/j.bioactmat.2025.08.004. eCollection 2025 Nov.
Androgenetic alopecia (AGA), the most prevalent form of hair loss, urgently requires breakthroughs in existing therapies due to limitations such as medication side effects, recurrence risks, and treatment inefficacy. Herein, we propose an insulin-derived self-assembling sequence Ac-GFFY, combined with the C domain peptide of insulin-like growth factor 1, successfully designing an IGF-1 biomimetic peptide factor, Ac-GFFY-IGF, which can substitute for the absent IGF-1 in the AGA pathological environment and facilitate hair regrowth. Compared with IGF-1, Ac-GFFY-IGF exhibits superior stability and enhanced skin permeability. In the murine AGA model, Ac-GFFY-IGF demonstrated superior efficacy to the clinically used minoxidil, achieving faster hair regeneration, higher hair quality, and broader hair coverage at lower concentrations. Our strategy provides a critical theoretical foundation and technical pathway for developing novel mechanism-driven therapies for AGA.
雄激素性脱发(AGA)是最常见的脱发形式,由于药物副作用、复发风险和治疗无效等局限性,现有治疗方法迫切需要取得突破。在此,我们提出了一种源自胰岛素的自组装序列Ac-GFFY,与胰岛素样生长因子1的C结构域肽相结合,成功设计出一种IGF-1仿生肽因子Ac-GFFY-IGF,它可以替代AGA病理环境中缺失的IGF-1并促进头发生长。与IGF-1相比,Ac-GFFY-IGF表现出更高的稳定性和增强的皮肤渗透性。在小鼠AGA模型中,Ac-GFFY-IGF显示出优于临床使用的米诺地尔的疗效,在较低浓度下能实现更快的毛发生长、更高的毛发质量和更广泛的毛发覆盖。我们的策略为开发针对AGA的新型机制驱动疗法提供了关键的理论基础和技术途径。