Xiong Sha, Li Zhongjun, Jiao Siwen, Xiao Ting, Wu Yan, Chen Chen, Guo Shiqi, Li Xiaojuan, Pan Zhiyuan, Li Jianqing, Xu Yuehong
School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China.
Faculty of Innovation Engineering, Macau University of Science and Technology, Macau, 999078, China.
J Nanobiotechnology. 2025 Feb 27;23(1):147. doi: 10.1186/s12951-025-03242-z.
Androgenetic alopecia (AGA), a chronic and progressive disease, significantly impacts the patients' social, emotional, and mental well-being. Current treatment for AGA are mainly limited by drug side effects and the stratum corneum (SC) barrier of scalp.
To address these issues, we developed a microneedle (MN) system loaded with black phosphorus nanosheets (BP) encapsulating baicalin (BA), a natural ingredient, for effective treatment of AGA. We first fabricated BP-BA based on the BP properties of high drug loading capacity and excellent photothermal conversion efficiency. Upon 635 nm laser irradiation, BP-BA demonstrated efficient photothermal conversion to mild thermal of ~ 42 °C. This mild thermal effect controlled BA's stimuli-responsive release, enhanced cellular uptake, and effectively modulated gene expression in dihydrotestosterone-treated human dermal papilla cells, downregulating negative regulators such as SRD5A2, AR, DKK1, and TGFB1, while upregulating positive regulators like CTNNBIP1 and VEGFA. Furthermore, we encapsulated BP-BA to MN fabricating BP-BA@MNs to overcome the SC barrier. Compared with BP-BA@MNs without laser irradiation, BP-BA@MNs with laser irradiation significantly enhanced drug penetration into the subcutaneous area and accumulation at the follicular site. Importantly, BP-BA@MNs demonstrated synergistic efficacy against testosterone-induced AGA in vivo through combining BA chemotherapy, BP-mediated mild photothermal therapy, and MN delivery, as well as good biocompatibility and biosafety, and the underlying synergistic mechanism was elucidated in terms of follicular microenvironment reconstruction.
This combining BP mild photothermal and MN system is a promising approach for follicular targeted drug delivery, providing a multifunctional strategy for addressing the clinical needs of anti-AGA.
雄激素性脱发（AGA）是一种慢性进行性疾病，对患者的社交、情感和心理健康有显著影响。目前AGA的治疗主要受药物副作用和头皮角质层（SC）屏障的限制。
为了解决这些问题，我们开发了一种微针（MN）系统，该系统负载有包裹黄芩苷（BA）的黑磷纳米片（BP），用于有效治疗AGA。我们首先基于BP的高载药能力和优异的光热转换效率制备了BP-BA。在635nm激光照射下，BP-BA表现出高效的光热转换，产生约42°C的温和热量。这种温和的热效应控制了BA的刺激响应释放，增强了细胞摄取，并有效地调节了经二氢睾酮处理的人真皮乳头细胞中的基因表达，下调了SRD5A2、AR、DKK1和TGFB1等负调节因子，同时上调了CTNNBIP1和VEGFA等正调节因子。此外，我们将BP-BA封装到MN中制备BP-BA@MNs以克服SC屏障。与未进行激光照射的BP-BA@MNs相比，进行激光照射的BP-BA@MNs显著增强了药物向皮下区域的渗透和在毛囊部位的积累。重要的是，BP-BA@MNs通过结合BA化疗、BP介导的温和光热疗法和MN递送，在体内对睾酮诱导的AGA表现出协同疗效，以及良好的生物相容性和生物安全性，并从毛囊微环境重建的角度阐明了潜在的协同机制。
这种结合BP温和光热和MN的系统是一种有前景的毛囊靶向给药方法，为满足抗AGA的临床需求提供了一种多功能策略。
