微泡
炎症性肠病
肿瘤坏死因子α
促炎细胞因子
生物利用度
小干扰RNA
口服
胃肠道
医学
癌症研究
炎症
药理学
免疫学
小RNA
化学
疾病
核糖核酸
内科学
基因
生物化学
作者
Geonhee Han,Hyo‐Suk Kim,Hochung Jang,Eun Sun Kim,Sun Hwa Kim,Yoosoo Yang
标识
DOI:10.1016/j.bioactmat.2023.12.010
摘要
Oral administration facilitates the direct delivery of drugs to lesions within the small intestine and colon, making it an ideal approach for treating patients with inflammatory bowel disease. However, multiple physical barriers impede the delivery of oral RNA drugs through the gastrointestinal tract. Herein, we developed a novel oral siRNA delivery system that protects nucleic acids in extreme environments by employing exosomes derived from milk to encapsulate tumor necrosis factor-alpha (TNF-α) siRNA completely. The remarkable structural stability of milk-derived exosomes (M-Exos), as opposed to those from HEK293T cells, makes them exceptional siRNA carriers. Results demonstrate that milk exosomes loaded with TNF-α siRNA (M-Exo/siR) can effectively inhibit the expression of TNF-α-related inflammatory cytokines. Moreover, given that milk exosomes are composed of unique lipids with high bioavailability, orally administered M-Exo/siR effectively reach colonic tissues, leading to decreased TNF-α expression and successful alleviation of colitis symptoms in a dextran sulfate sodium-induced inflammatory bowel disease murine model. Hence, milk-derived exosomes carrying TNF-α siRNA can be effectively employed to treat inflammatory bowel disease. Indeed, using exosomes naturally derived from milk may shift the current paradigm of oral gene delivery, including siRNA.
科研通智能强力驱动
Strongly Powered by AbleSci AI