Journal
ACTA PHARMACEUTICA SINICA B
Volume 12, Issue 8, Pages 3367-3382Publisher
INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
DOI: 10.1016/j.apsb.2022.03.025
Keywords
Polyphenol; mRNA; IL-10; Colitis; Inflammatory bowel disease; Drug delivery; mRNA delivery; Supramolecular binding
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Funding
- Science and Technology Development Fund, Macau SAR (China) [00151/2020/A3, SKL-QRCM(UM)2020-2022]
- Major Basic and Applied Basic Research Projects of Guangdong Province of China [2019B030302005]
- Guangxi Science and Technology Research Project (China) [GuiKeAA18242040]
- University of Macau (China) [MYRG2020-00141-ICMS, EF013/ICMS-WYT/2019/GPU]
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With the assistance of polyphenols, a handy delivery strategy has been proposed for efficient in vivo delivery of IL-10 mRNA, showing potential for the treatment of ulcerative colitis.
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. (C) 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
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