Huili Wang, Zhijia Li, Yuanxi Mo, Asher Ruien Lau, Qian Huang, Yuxing Wang, Yan Zhang, Ziyu Ning, Mingjing Zhou, Muzhou Teng, Yingjun Ouyang, Xiaojun Liu, Wenya Li, Hongrui Qiu, Bowen Zhu, Weihai Liang, Chun Yang, Hsuan Lo, Chenyi Xie, Shiying Li
Plant-derived exosome-like nanoparticles (PDENs) are emerging as biocompatible and effective drug delivery systems. Proanthocyanidins (Pro), potent antioxidants, scavenge reactive oxygen species (ROS) and inhibit matrix metalloproteinases (MMPs), which are key mediators of skin aging. In this study, we developed a ginseng root-derived exosome-based formulation encapsulating proanthocyanidins (Pro@Gin-Exo) for microneedle roller-assisted prevention of ultraviolet (UV)-induced skin photoaging. The Pro@Gin-Exo nanoplatforms were fabricated using a novel microfluidic strategy that facilitates membrane fusion between exosomes and proanthocyanidin-loaded liposomes, yielding highly uniform nanoparticles with excellent colloidal stability and hemocompatibility. The formulation exerted significant anti-photoaging effects primarily by suppressing ROS and inhibiting MMP-2. In a chronic UV-induced photoaging mouse model, microneedle roller-assisted delivery of Pro@Gin-Exo significantly suppressed wrinkle formation, increased epidermal and dermal thickness, and restored collagen density, without detectable toxicity. Consistent with these preclinical results, a pilot human study involving 30 volunteers (average age: 47 years) demonstrated that one month of Pro@Gin-Exo treatment significantly improved skin smoothness, elasticity, hydration, wrinkle depth, pigmentation, and pore size compared to the control group. In conclusion, this study establishes a nanoplatform that integrates Gin-Exo with liposomes loaded with plant-derived bioactive compounds, utilizing microneedle rollers to enhance skin permeation. Both animal and initial human studies confirmed the safety and efficacy of the Pro@Gin-Exo nanoplatforms, supporting their potential as a translatable therapeutic strategy for skin regeneration and photoaging prevention. Ginseng root-derived exosome-coated proanthocyanidins (Pro@Gin-Exo), fabricated via a microfluidic membrane-fusion strategy, show excellent stability, safety, and enhanced skin delivery when combined with microneedles. In both UV-induced photoaging mice and a human pilot study, Pro@Gin-Exo treatment significantly improved skin structure and appearance, demonstrating strong potential for anti-photoaging therapy.