School of Food and Biological Engineering, Hefei University of Technology, Hefei, 230009, China.
School of Biomedical Engineering, Anhui Medical University, Hefei, 230032, China.
Nat Commun. 2024 Sep 28;15(1):8428. doi: 10.1038/s41467-024-52722-7.
Excessive accumulation of reactive oxygen and nitrogen species (RONS) and dysbiosis of intestinal microbiota are pivotal symptoms for inflammatory bowel disease (IBD) and its associated complications, such as intestinal fibrosis. This research introduces a probiotic inulin hydrogel loaded with polypyrrole (PPy) nanozymes and antifibrotic drug pirfenidone (PFD) (PPy/PFD@Inulin gel) designed for the concurrent amelioration of IBD and its fibrotic complication. Upon oral administration, the inulin gel matrix could extend the gastrointestinal residence time of PPy nanozymes and PFD, facilitating the efficient reduction of pro-inflammatory cytokine levels and enhancement of the intestinal epithelial barrier repair as well as the suppression of intestinal fibrosis through sustained RONS scavenging, modulation of gut microbiota and attenuation of the TGF-β/Smad signaling pathway to inhibit fibroblast proliferation. Notably, the PPy/PFD@Inulin gel demonstrated significant prophylactic and therapeutic efficacy in acute and chronic colitis as well as intestinal fibrosis induced by dextran sodium sulfate (DSS) in mouse models. Thus, the engineered ternary PPy/PFD@Inulin gel offered a pioneered paradigm for simultaneous reversal of IBD and its associated complications, such as intestinal fibrosis, in a single therapeutic regimen.
活性氧和氮物种（RONS）的过度积累以及肠道微生物群落失调是炎症性肠病（IBD）及其相关并发症（如肠道纤维化）的关键症状。本研究介绍了一种载有聚吡咯（PPy）纳米酶和抗纤维化药物吡非尼酮（PFD）的益生菌菊粉水凝胶（PPy/PFD@Inulin gel），旨在同时改善 IBD 及其纤维化并发症。口服后，菊粉凝胶基质可以延长 PPy 纳米酶和 PFD 的胃肠道驻留时间，通过持续清除活性氧和氮物种、调节肠道微生物群落以及抑制 TGF-β/Smad 信号通路来抑制成纤维细胞增殖，从而有效降低促炎细胞因子水平、增强肠道上皮屏障修复并抑制肠道纤维化。值得注意的是，PPy/PFD@Inulin 水凝胶在 DSS 诱导的急性和慢性结肠炎以及肠道纤维化小鼠模型中表现出显著的预防和治疗效果。因此，该工程化的三元 PPy/PFD@Inulin 水凝胶为单一治疗方案同时逆转 IBD 及其相关并发症（如肠道纤维化）提供了开创性的范例。
