A polyphenol-assisted IL-10 mRNA delivery system for ulcerative colitis.
10.1016/j.apsb.2022.03.025
- Author:
Zhejie CHEN
1
;
Wei HAO
1
;
Caifang GAO
1
;
Yangyang ZHOU
1
;
Chen ZHANG
2
;
Jinming ZHANG
2
;
Ruibing WANG
1
;
Yitao WANG
1
;
Shengpeng WANG
1
Author Information
1. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China.
2. College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
- Publication Type:Journal Article
- Keywords:
Colitis;
Drug delivery;
IL-10;
Inflammatory bowel disease;
Polyphenol;
Supramolecular binding;
mRNA;
mRNA delivery
- From:
Acta Pharmaceutica Sinica B
2022;12(8):3367-3382
- CountryChina
- Language:English
-
Abstract:
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.
