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仿生超分子组装与 IGF-1C 递呈通过恢复肠道屏障完整性改善炎症性肠病（IBD）。

Biomimetic Supramolecular Assembly with IGF-1C Delivery Ameliorates Inflammatory Bowel Disease (IBD) by Restoring Intestinal Barrier Integrity.

机构信息

School of Medicine, Nankai University, Tianjin, 300071, China.

Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, 300071, China.

出版信息

Adv Sci (Weinh). 2024 Sep;11(36):e2403075. doi: 10.1002/advs.202403075. Epub 2024 Jul 23.

DOI:10.1002/advs.202403075
PMID:39041890
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11423171/
Abstract

The management of dysfunctional intestinal epithelium by promoting mucosal healing and modulating the gut microbiota represents a novel therapeutic strategy for inflammatory bowel disease (IBD). As a convenient and well-tolerated method of drug delivery, intrarectal administration may represent a viable alternative to oral administration for the treatment of IBD. Here, a biomimetic supramolecular assembly of hyaluronic acid (HA) and β-cyclodextrin (HA-β-CD) for the delivery of the C domain peptide of insulin-like growth factor-1 (IGF-1C), which gradually releases IGF-1C, is developed. It is identified that the supramolecular assembly of HA-β-CD enhances the stability and prolongs the release of IGF-1C. Furthermore, this biomimetic supramolecular assembly potently inhibits the inflammatory response, thereby restoring intestinal barrier integrity. Following HA-β-CD-IGF-1C administration, 16S rDNA sequencing reveals a significant increase in the abundance of the probiotic Akkermansia, suggesting enhanced intestinal microbiome homeostasis. In conclusion, the findings demonstrate the promise of the HA-based mimicking peptide delivery platform as a therapeutic approach for IBD. This biomimetic supramolecular assembly effectively ameliorates intestinal barrier function and intestinal microbiome homeostasis, suggesting its potential for treating IBD.

摘要

通过促进黏膜愈合和调节肠道微生物群来管理功能失调的肠上皮，代表了一种治疗炎症性肠病（IBD）的新的治疗策略。作为一种方便且耐受性良好的药物输送方法，直肠内给药可能是治疗 IBD 的口服给药的可行替代方法。在这里，开发了一种透明质酸（HA）和β-环糊精（HA-β-CD）的仿生超分子组装体，用于递送电胰岛素样生长因子-1（IGF-1C）的 C 域肽，其逐渐释放 IGF-1C。已经确定，HA-β-CD 的超分子组装增强了 IGF-1C 的稳定性并延长了其释放。此外，这种仿生超分子组装能够强烈抑制炎症反应，从而恢复肠道屏障完整性。在 HA-β-CD-IGF-1C 给药后，16S rDNA 测序显示益生菌 Akkermansia 的丰度显着增加，表明肠道微生物组的稳态得到增强。总之，这些发现表明基于 HA 的模拟肽递药平台作为 IBD 的治疗方法具有广阔的前景。这种仿生超分子组装可有效改善肠道屏障功能和肠道微生物组稳态，表明其在治疗 IBD 方面具有潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d3e/11423171/4f4f3c009c20/ADVS-11-2403075-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d3e/11423171/fb9f14e77b5d/ADVS-11-2403075-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d3e/11423171/895575f1840a/ADVS-11-2403075-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d3e/11423171/4f4f3c009c20/ADVS-11-2403075-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d3e/11423171/fb9f14e77b5d/ADVS-11-2403075-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d3e/11423171/ae1523de8be1/ADVS-11-2403075-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d3e/11423171/8028a424b816/ADVS-11-2403075-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d3e/11423171/513c56ded9f9/ADVS-11-2403075-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d3e/11423171/895575f1840a/ADVS-11-2403075-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d3e/11423171/4f4f3c009c20/ADVS-11-2403075-g003.jpg

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