Oxidative Stress and Hormone-Regulated Dermal Papilla Cell-Targeted Nanomodulators: Reverse Cellular Senescence for Androgenetic Alopecia Therapy

Androgenetic alopecia (AGA), a prevalent form of hair loss disorder, is pathologically characterized by dermal papilla cell (DPC) senescence driven by the dual pathogenic effects of excessive dihydrotestosterone accumulation and reactive-oxygen-species-mediated oxidative stress. Current clinical treatment strategies are challenged by poor hair follicle targeting, short retention times, and limited efficacy due to single-pathway interventions. To address these limitations, we developed a DPC-targeted, dual-functional finasteride/cerium oxide nanoparticle (L-LP-Fi/CeNP) drug delivery system designed to synergistically counteract DPC senescence through concurrent dihydrotestosterone inhibition and reactive oxygen species scavenging. By actively targeting the DPC-specific surface marker leptin receptor, this system notable enhanced cutaneous penetration depth and prolonged intrafollicular drug retention. Within the pathological microenvironment, the combined action of finasteride and CeNPs down-regulated senescence markers (p16/pRb) via dual-pathway synergy, effectively reversing cellular senescence and restoring the hair-inductive capacity of DPCs. In AGA mouse models, L-LP-Fi/CeNPs exhibited hair regenerative efficacy comparable to, and in some aspects modestly improved over, that of minoxidil, the current clinical standard treatment. This study presents a novel targeted therapeutic strategy combining small-molecule drug synergism with nanotechnology, which offers a promising prospect for AGA treatment.