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病理性催化物理涂层修复肠屏障治疗炎症性肠病。

Pathologically catalyzed physical coating restores the intestinal barrier for inflammatory bowel disease therapy.

机构信息

Shanghai Tenth People's Hospital, The Institute for Biomedical Engineering & Nano Science (iNANO), School of Medicine, Tongji University, Shanghai, 200092, China.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

出版信息

J Nanobiotechnology. 2023 Nov 24;21(1):444. doi: 10.1186/s12951-023-02227-0.

DOI:10.1186/s12951-023-02227-0
PMID:37996883
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10668504/
Abstract

Intestinal epithelia impairment of inflammatory bowel disease (IBD) leads to the leakage of bacteria and antigens and the consequent persistent immune imbalance. Restoring the epithelial barrier is a promising therapeutic target but lacks effective and safe clinical interventions. By identifying the catalase (CAT) presence in the IBD pathological environment, we herein develop a CAT-catalyzed pathologically coating on the damaged epithelial barrier to inhibit intestinal leakage for IBD therapy. With the codelivery of CaO (a CAT substrate) and dopamine, the nanosystem can enable CAT-catalyzed oxygen (O) production and in-situ polymerization of dopamine and then yield a thin and integrative polydopamine (PDA) coating on the intestinal barrier due to the highly adhesive property of PDA. In vivo study demonstrates that PDA coating provides not only a protective barrier by restricting intestinal leakage but also a favorable anti-inflammation effect. Beyond drug management, this work provides a physical repair strategy via catalyzed coating for IBD therapy.

摘要

肠上皮细胞损伤是炎症性肠病(IBD)的主要原因,会导致细菌和抗原的渗漏,进而引起持续的免疫失衡。修复上皮屏障是一种很有前途的治疗靶点,但目前缺乏有效和安全的临床干预措施。通过在 IBD 病理环境中鉴定出过氧化氢酶(CAT)的存在,我们在此开发了一种 CAT 催化的病理涂层,以抑制 IBD 治疗中的肠道渗漏。通过共递送 CaO(CAT 的底物)和多巴胺,该纳米系统能够实现 CAT 催化的氧气(O)生成和多巴胺的原位聚合,然后由于 PDA 的高粘附性,在肠屏障上生成一层薄且整合的聚多巴胺(PDA)涂层。体内研究表明,PDA 涂层不仅提供了一个限制肠道渗漏的保护屏障,而且还具有良好的抗炎作用。除了药物管理,这项工作还通过催化涂层为 IBD 治疗提供了一种物理修复策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37d1/10668504/bbc220b1fc3c/12951_2023_2227_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37d1/10668504/cb67229b10cf/12951_2023_2227_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37d1/10668504/05bba74fc3ff/12951_2023_2227_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37d1/10668504/98a0914c1a8e/12951_2023_2227_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37d1/10668504/19e520809956/12951_2023_2227_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37d1/10668504/a26024a6c45e/12951_2023_2227_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37d1/10668504/bbc220b1fc3c/12951_2023_2227_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37d1/10668504/cb67229b10cf/12951_2023_2227_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37d1/10668504/b7b9a8d47385/12951_2023_2227_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37d1/10668504/05bba74fc3ff/12951_2023_2227_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37d1/10668504/98a0914c1a8e/12951_2023_2227_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37d1/10668504/19e520809956/12951_2023_2227_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37d1/10668504/a26024a6c45e/12951_2023_2227_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37d1/10668504/bbc220b1fc3c/12951_2023_2227_Fig7_HTML.jpg

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