Inhibition of Transmural Inflammation in Crohn’s Disease by Orally Administered Tumor Necrosis Factor-Alpha Deoxyribozymes-Loaded Pyroptosis Nanoinhibitors

作者：Zhun Li, Zhenxing Zhu, Dongtao Zhou, Yusheng Chen, Yi Yin, Zhibin Zhang, Jingjing Yang, Yanfeng Gao, Weiming Zhu, Yujun Song, Yi Li · 发表于：ACS Applied Materials & Interfaces · 年份：2024 · DOI：10.1021/acsami.4c05921 · 被引用次数：6 · 研究领域：Inflammasome and immune disorders、Inflammatory Bowel Disease、Autoimmune and Inflammatory Disorders Research

Crohn's disease (CD) is a refractory chronic inflammatory bowel disease (IBD) with unknown etiology. Transmural inflammation, involving the intestine and mesentery, represents a characteristic pathological feature of CD and serves as a critical contributor to its intractability. Here, this study describes an oral pyroptosis nanoinhibitor loaded with tumor necrosis factor-α (TNF-α) deoxyribozymes (DNAzymes) (DNAzymes@degradable silicon nanoparticles@Mannose, Dz@MDSN), which can target macrophages at the site of inflammation and respond to reactive oxygen species (ROS) to release drugs. Dz@MDSN can not only break the inflammatory cycle in macrophages by degrading TNF-α mRNA but also reduce the production of ROS mainly from macrophages. Moreover, Dz@MDSN inhibits excessive pyroptosis in epithelial cells through ROS clearance, thereby repairing the intestinal barrier and reducing the translocation of intestinal bacteria to the mesentery. Consequently, these combined actions synergistically contribute to the suppression of inflammation within both the intestine and the mesentery. This study likely represents the first successful attempt in the field of utilizing nanomaterials to achieve transmural healing for CD, which also provides a promising treatment strategy for CD patients.