Beijing Laboratory of Biomedical Materials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, China.
CAS Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China.
ACS Appl Mater Interfaces. 2023 Jul 5;15(26):31214-31223. doi: 10.1021/acsami.3c04408. Epub 2023 Jun 20.
Oral delivery of probiotics has been a promising method for treatment of inflammatory bowel diseases (IBDs). However, probiotics always suffer from substantial loss of viability due to the harsh gastrointestinal conditions, especially the highly acidic environment in the stomach and bile salts in the intestine. In addition, to overcome the challenging conditions, an ideal delivery of probiotics requires the on-demand release of probiotics upon environmental response. Herein, a novel nitroreductase (NTR) labile peptidic hydrogel based on supramolecular self-assembly is demonstrated. The efficient encapsulation of typical probiotic (EcN) into supramolecular assemblies yielded a probiotic-loaded hydrogel (EcN@Gel). Such a hydrogel adequately protected EcN to improve its viability against harsh acid and bile salt environments during oral delivery. The upregulated NTR in the intestinal tract triggered the disassembly of the hydrogel and accomplished the controlled release of EcN locally. In ulcerative colitis (UC)-bearing mice, EcN@Gel showed significantly enhanced therapeutic efficacy by downregulating proinflammatory cytokines and repairing the intestinal barrier. Moreover, EcN@Gel remolded the gut microbiome by increasing the diversity and abundance of indigenous probiotics, contributing to ameliorated therapies of IBDs. The NTR-labile hydrogel provided a promising platform for the on-demand delivery of probiotics into the intestinal tract.
口服递送益生菌一直是治疗炎症性肠病（IBD）的一种很有前景的方法。然而，由于胃肠道环境恶劣，特别是胃酸和肠道胆汁盐的存在，益生菌的存活率往往会受到很大的影响。此外，为了克服这些挑战性的条件，理想的益生菌递送需要在环境响应时按需释放益生菌。本文中，作者展示了一种基于超分子自组装的新型硝基还原酶（NTR）不稳定肽类水凝胶。典型益生菌（EcN）的高效包封到超分子组装体中，得到了负载益生菌的水凝胶（EcN@Gel）。这种水凝胶能够充分保护 EcN，提高其在口服递送过程中抵抗恶劣酸和胆汁盐环境的生存能力。肠道中上调的 NTR 触发水凝胶的解组装，并实现 EcN 的局部控制释放。在溃疡性结肠炎（UC）荷瘤小鼠中，EcN@Gel 通过下调促炎细胞因子和修复肠道屏障，显示出显著增强的治疗效果。此外，EcN@Gel 通过增加本土益生菌的多样性和丰度来重塑肠道微生物组，有助于改善 IBD 的治疗效果。NTR 不稳定水凝胶为益生菌按需递送到肠道提供了一个很有前途的平台。
