Cross-kingdom delivery and putative gene modulation of androgen pathways by plant-derived exosome-like nanoparticles from polygoni multiflori radix promotes hair growth via miRNA cargo

作者：Shaojin Li, You-Bo Zhang, Xiyang Liu, Huang Su, Haiyan Cao, Hong Xuan, Yingxian Cui, Ziang Lu, qinhao zhang, Yike Li, Yike Li, Xiaoai Bao, Hailong Xu, Yanlin Wang, Xinjie Zhuo, Xinyue Zhang, Qingying Zhang, Qingying Zhang · 发表于：Pharmacological Research · 年份：2025 · DOI：10.1016/j.phrs.2025.108033 · 被引用次数：10 · 研究领域：Hair Growth and Disorders、Advancements in Transdermal Drug Delivery、Skin and Cellular Biology Research

Plant-derived exosome-like nanoparticles (PENs) have emerged as promising nanocarriers for cross-kingdom delivery and putative gene modulation, yet their functional role in human physiology remains largely unexplored. Here, we isolate and characterize exosome-like nanoparticles from Polygoni Multiflori Radix (PMENs) and demonstrate their capacity to promote hair growth through cross-kingdom delivery and putative gene modulation of androgen signaling. PMENs are efficiently internalized by dermal papilla cells via caveolin- and heparan sulfate proteoglycan-mediated endocytosis, delivering plant-derived miRNAs that directly target the human androgen receptor (AR). This leads to downregulation of AR expression and downstream suppression of DKK1, a key inhibitor of the Wnt/β-catenin pathway. PMENs concurrently increase GSK3β phosphorylation and stabilize β-catenin, fostering hair follicle regeneration. In testosterone-induced delay in hair regrowth in C57BL/6 mice, PMENs outperform Minoxidil in restoring hair growth. High-throughput sequencing identifies aof-miR168a and osa-miR164a as core miRNA effectors, confirmed to repress AR via conserved 3'UTR binding sites. These findings establish PMENs as a novel, miRNA-mediated nanotherapy that enables putative cross-kingdom gene modulation and provides a compelling strategy for treating androgen-driven conditions such as AGA.