Sustainability of functional hair follicle activity: Impact of spatially anchored multifunctional tetrahedral framework nucleic acids

Alopecia is a physical and mental health problem affecting all age groups, aesthetically or psychologically. Among its subtypes, androgenetic alopecia (AGA) is the most prevalent. This androgen-dependent, polygenic disease is hereditary and can occur as early as adolescence. Currently available therapies remain largely palliative and are often accompanied by adverse side effects. Here, we constructed a multifunctional system based on tetrahedral framework nucleic acids (tFNAs), in which quercetin was embedded within tFNAs to form a complex termed tFNAs-Que (TQC). We performed multimodal analysis, combined with transcriptomic analysis, to explore the activation and sustainable changes in the hair follicle cycle after TQC treatment. Our results showed that TQC maintained the stability of the epithelial structure and enhanced the regeneration of functional hair follicles by regulating both hair follicle stem cells (HFSCs) and dermal papilla cells (DPCs). Additionally, we identified a catalytic role of tFNAs. Overall, this study developed a dual-regulated nucleic acid nanoparticle, opening up new avenues for clinical translation in activating, stabilizing, and sustaining the hair cycle.