Orally-Delivered, Cytokine-Engineered Extracellular Vesicles for Targeted Treatment of Inflammatory Bowel Disease

被引：23

作者：

Liu, Jingang ^{[1
]}

Ren, He ^{[1
]}

Zhang, Chen ^{[1
]}

Li, Jiexin ^{[1
]}

Qiu, Qian ^{[1
]}

Zhang, Nan ^{[1
]}

Jiang, Ning ^{[2
]}

Lovell, Jonathan F. ^{[3
]}

Zhang, Yumiao ^{[1
]}

机构：

[1] Tianjin Univ, Frontiers Sci Ctr Synthet Biol, Sch Chem Engn & Technol, Key Lab Syst Bioengn,Minist Educ, Tianjin 300350, Peoples R China

[2] South China Univ Technol, Sch Biol & Biol Engn, Guangzhou 510006, Peoples R China

[3] State Univ New York Buffalod, Dept Biomed Engn, Buffalo, NY 14260 USA

来源：

SMALL | 2023年 / 19卷 / 50期

基金：

中国国家自然科学基金;

关键词：

extracellular vesicles; galactose; inflammatory bowel disease; interleukin; 10; oral protein administration; CHITOSAN-ALGINATE NANOPARTICLES; LACTOCOCCUS-LACTIS; HUMAN MONOCYTES; IL-10; THERAPY; COLITIS; INTERLEUKIN-10; EXOSOMES; SECRETION; BIOLOGY;

D O I：

10.1002/smll.202304023

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The use of orally-administered therapeutic proteins for treatment of inflammatory bowel disease (IBD) has been limited due to the harsh gastrointestinal environment and low bioavailability that affects delivery to diseased sites. Here, a nested delivery system, termed Gal-IL10-EVs (C/A) that protects interleukin 10 (IL-10) from degradation in the stomach and enables targeted delivery of IL-10 to inflammatory macrophages infiltrating the colonic lamina propria, is reported. Extracellular vesicles (EVs) carrying IL-10 are designed to be secreted from genetically engineered mammalian cells by a plasmid system, and EVs are subsequently modified with galactose, endowing the targeted IL-10 delivery to inflammatory macrophages. Chitosan/alginate (C/A) hydrogel coating on Gal-IL10-EVs enables protection from harsh conditions in the gastrointestinal tract and favorable delivery to the colonic lumen, where the C/A hydrogel coating is removed at the diseased sites. Gal-IL10-EVs control the production of reactive oxygen species (ROS) and inhibit the expression of proinflammatory cytokines. In a murine model of colitis, Gal-IL10-EVs (C/A) alleviate IBD symptoms including inflammatory responses and disrupt colonic barriers. Taken together, Gal-IL10-EVs (C/A) features biocompatibility, pH-responsive drug release, and macrophage-targeting as a therapeutic platform for oral delivery of bioactive proteins for treating intestinal diseases. A nested delivery system for oral delivery of the anti-inflammatory cytokine IL-10 for the treatment of inflammatory bowel disease is developed. The new method for orally taking protein has high patient compliance, compared with intravenous or intramuscular administration routes. This proof-of-concept for IBD treatment also affords a versatile methodology for other oral protein-based therapeutics delivery.image

引用

页数：13

共 67 条

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