Amphiphilic Covalent Organic Framework for Efficient DHT Adsorption and Androgenetic Alopecia Treatment via Spectral...

Androgenetic alopecia (AGA) is a prevalent clinical disorder, and the key pathogenic factor is dihydrotestosterone (DHT) present in the pilosebaceous unit. Current clinical therapeutic options are often associated with notable adverse effects, highlighting the urgent need for safer and more effective interventions. Herein, a novel amphiphilic covalent organic framework (amCOF) is designed and synthesized. By simultaneously incorporating hydrophilic functional groups and lipophilic alkyl chains into the covalent organic skeleton, the material exhibits excellent amphiphilicity, high specific surface area, and well-ordered porous structures. Owing to its amphiphilic nature, amCOF disperses uniformly in aqueous physiological media and adapts favorably to the lipophilic microenvironment within hair follicles. Furthermore, the ordered porous architecture endows amCOF with rapid DHT adsorption kinetics, high adsorption capacity, and high removal efficiency. Functional assays demonstrate that amCOF effectively reverses the inhibitory effects of DHT on the proliferation and migration of human dermal papilla cells. In animal models, topical application of amCOF significantly reduces local DHT concentrations, promotes hair regrowth, and shows favorable biosafety profiles. Collectively, this work provides a new strategy for treating androgenetic alopecia by scavenging pathogenic lipophilic molecules from sebum using amphiphilic porous materials and also establishes a solid foundation for expanding the biomedical applications of COFs.