摘要
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.
基金
funded by the Science and Technology Development Fund,Macao SAR (00151/2020/A3 & SKL-QRCM(UM)2020-2022,China)
Major Basic and Applied Basic Research Projects of Guangdong Province of China (2019B030302005)
Guangxi Science and Technology Research Project (GuiKe AA18242040,China)
the University of Macao (MYRG2020-00141-ICMS and EF013/ICMS-WYT/2019/GPU,China)。
