A polyphenol-assisted IL-10 mRNA delivery system for ulcerative colitis

Autor: Zhejie Chen, Wei Hao, Caifang Gao, Yangyang Zhou, Chen Zhang, Jinming Zhang, Ruibing Wang, Yitao Wang, Shengpeng Wang
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Acta Pharmaceutica Sinica B, Vol 12, Iss 8, Pp 3367-3382 (2022)
Druh dokumentu: article
ISSN: 2211-3835
DOI: 10.1016/j.apsb.2022.03.025
Popis: With the development of synthesis technology, modified messenger RNA (mRNA) has emerged as a novel category of therapeutic agents for a broad of diseases. However, effective intracellular delivery of mRNA remains challenging, especially for its sensitivity to enzymatic degradation. Here, we propose a polyphenol-assisted handy delivery strategy for efficient in vivo delivery of IL-10 mRNA. IL-10 mRNA binds to polyphenol ellagic acid through supramolecular binding to yield a negatively charged core, followed by complexing with linear polyetherimide and coating with bilirubin-modified hyaluronic acid to obtain a layer-by-layer nanostructure. The nanostructure specifically up-regulated the level of IL-10, effectively inhibited the expression of inflammatory factors, promoted mucosal repair, protected colonic epithelial cells against apoptosis, and exerted potent therapeutic efficacy in dextran sulfate sodium salt-induced acute and chronic murine models of colitis. The designed delivery system without systemic toxicity has the potential to facilitate the development of a promising platform for mRNA delivery in ulcerative colitis treatment.
Databáze: Directory of Open Access Journals