细胞凋亡
炎症性肠病
癌症研究
医学
纳米医学
细胞
疾病
胃肠病学
生物
内科学
材料科学
纳米技术
生物化学
纳米颗粒
作者
Mingyuan Wang,Qiong Huang,Min Liu,Tianjiao Zhao,Xiangping Song,Qiaohui Chen,Yongqi Yang,Yayun Nan,Zerun Liu,Yuntao Zhang,Wei Wu,Kelong Ai
标识
DOI:10.1002/adma.202309370
摘要
The increased incidence of inflammatory bowel disease (IBD) has seriously affected the life quality of patients. IBD develops due to excessive intestinal epithelial cell (IEC) apoptosis, disrupting the gut barrier, colonizing harmful bacteria, and initiating persistent inflammation. The current therapeutic approaches that reduce inflammation are limited. Although IBD can be treated significantly by directly preventing IEC apoptosis, achieving this therapeutic approach remains challenging. Accordingly, the authors are the first to develop an oral pifithrin-α (PFTα, a highly specific p53 inhibitor) embedded nanomedicine (OPEN) to effectively treat IBD by inhibiting excessive IEC apoptosis. As a major hub for various stressors, p53 is a central determinant of cell fate, and its inhibition can effectively reduce excessive IEC apoptosis. The tailored OPEN can precisely inhibit the off-target and inactivation resulting from PFTα entry into the bloodstream. Subsequently, it persistently targets IBD lesions with high specificity to inhibit the pathological events caused by excessive IEC apoptosis. Eventually, OPEN exerts a significant curative effect compared with the clinical first-line drugs 5-aminosalicylic acid (5-ASA) and dexamethasone (DEX). Consequently, the OPEN therapeutic strategy provides new insights into comprehensive IBD therapy.
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