Zhou Hong, Zhang Shuting, Liu Xinxin, Feng Aiping, Chen Siyuan, Liu Wei
National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China.
Acta Pharm Sin B. 2025 Apr;15(4):2197-2216. doi: 10.1016/j.apsb.2025.02.038. Epub 2025 Mar 7.
Due to the difficulty of overcoming the abnormal epidermal barriers and addressing infections without disrupting indigenous skin microbiota, effective treatment of bacterial infection atopic dermatitis (AD) remains a significant clinical challenge. Skin microbiota-derived extracellular vesicles (EVs) shows protentional for skin disease treatment, but the lack of antimicrobial activity and limited skin penetration hamper their application in bacterial infection AD treatment. Here, we developed novel nanoantibiotics by loading Lev into derived EVs (Lev@SE-EVs), with supreme antimicrobial activity, regulating epidermal immune responses and enhanced epidermal barrier functionality. The nanoantibiotics were further integrated into hyaluronic acid-based microneedle (MN) for efficient transdermal delivery of therapeutic agents and effectively treating bacterial infection in AD. Upon insertion into the skin, the rapidly released Lev@SE-EVs from MN are uptake by in a selective manner, fibroblasts, and surrounding immune cells to exert therapeutic effects in the infected dermal layer, resulting in mitigated skin inflammation, reduced burden and increased dermis repair. Notably, Lev@SE-EVs induce IL-17A CD8 T-cell accumulation in the skin in an unrelated inflammation manner, which may represent heterologous protection. This EVs-integrated MN assisted Lev@SE-EVs to alleviate skin inflammation, repair skin, and provide an effective and safe therapeutic approach for bacterial infection AD treatment.
由于克服异常表皮屏障以及在不破坏皮肤固有微生物群的情况下解决感染存在困难，特应性皮炎（AD）细菌感染的有效治疗仍然是一项重大的临床挑战。皮肤微生物群衍生的细胞外囊泡（EVs）在皮肤病治疗方面显示出潜力，但缺乏抗菌活性和有限的皮肤渗透性阻碍了它们在AD细菌感染治疗中的应用。在此，我们通过将左氧氟沙星（Lev）负载到衍生的EVs（Lev@SE-EVs）中开发了新型纳米抗生素，其具有卓越的抗菌活性，可调节表皮免疫反应并增强表皮屏障功能。该纳米抗生素进一步整合到基于透明质酸的微针（MN）中，以实现治疗剂的高效透皮递送并有效治疗AD中的细菌感染。插入皮肤后，从MN快速释放的Lev@SE-EVs被成纤维细胞和周围免疫细胞以选择性方式摄取，从而在感染的真皮层发挥治疗作用，减轻皮肤炎症，减轻负担并促进真皮修复。值得注意的是，Lev@SE-EVs以不相关的炎症方式诱导皮肤中IL-17A CD8 T细胞积累，这可能代表异源保护。这种整合了EVs的MN协助Lev@SE-EVs减轻皮肤炎症、修复皮肤，并为AD细菌感染治疗提供了一种有效且安全的治疗方法。
