近日,沈阳药科大学
口腔表面修饰的益生菌疗法能够在恶劣的胃肠道条件下保持益生菌的活性和粘附性,是治疗溃疡性结肠炎(UC)的有效方法。然而,目前报道的表面修饰益生菌由于不同的物理化学性质,在病变部位的选择性定植能力差,与其他治疗方式的共递送能力有限。
研究组开发了可触发的益生菌-药物偶联物,使它们能够同步位点特异性益生菌定植和按需药物释放,用于治疗UC及其并发症。具体而言,偶联物由益生菌大肠杆菌Nissle 1917和活性氧(ROS)响应的硫醚桥接翼苯乙烯-脂质外涂层组成。经口服后,病理性高水平ROS可触发炎症结肠中偶联物的抗炎紫檀芪和粘附性益生菌的适应性释放。粘附性益生菌的靶向定植,与紫檀芪同步结合在病变部位,实现炎症抑制和持续的肠道微生物群调节。在UC和相关并发症的无主题模型中,该缀合物显示出显著的治疗和预防功效,突出了其在胃肠道疾病临床联合应用的转化潜力。
附:英文原文
Title: Probiotic–Drug Conjugates Achieve Synchronized Site-Specific Probiotic Colonization and On-Demand Drug Release against Ulcerative Colitis and Its Complication
Author: Linzhou Yin, Shuwen Han, Jiang Xiaowen, Jie Liu, Zhichao Chen, Xi Yang, Zhonggui He, Mengchi Sun, Jin Sun, Huiyuan Gao
Issue&Volume: August 12, 2025
Abstract: The oral surface-modified probiotic therapy, capable of maintaining activity and adhesion of probiotics under harsh gastrointestinal conditions, is effective in treating ulcerative colitis (UC). However, the currently reported surface-modified probiotics suffer from poor selective colonization at a lesion site and limited codelivery capability with other treatment modalities due to different physicochemical properties. Herein, we develop triggerable probiotic–drug conjugates that enable synchronous site-specific probiotic colonization and on-demand drug release for the treatment of UC and its complication. Specifically, the conjugates are composed of probiotic Escherichia coli Nissle 1917 encapsulated with the adhesive tannic acid-ferric inner layer and the reactive oxygen species (ROS)-responsive thioether-bridged pterostilbene-lipid outer coating. Following oral administration, the pathological high-level ROS can trigger the adaptable release of anti-inflammatory pterostilbene and adhesive probiotics from conjugates in the inflamed colon. The targeted colonization of adhesive probiotics, combined with pterostilbene at the lesion site in a synchronous manner, achieves inflammation suppression and sustained gut microbiota modulation. In both mouse models of UC and associated complications, this conjugate demonstrates significant therapeutic and prophylactic efficacy, highlighting its translational potential for clinical combined applications in gastrointestinal disorders.
DOI: 10.1021/jacs.5c08094
Source: https://pubs.acs.org/doi/abs/10.1021/jacs.5c08094
JACS:《美国化学会志》,创刊于1879年。隶属于美国化学会,最新IF:16.383
官方网址:https://pubs.acs.org/journal/jacsat
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