Oral administration of Sophora Flavescens-derived exosomes-like nanovesicles carrying CX5461 ameliorates DSS-induced colitis in mice.

Autor: Zhang M; School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Gongchang Road, Shenzhen, Guangdong, 518107, China., Xu X; Endoscopy Center and Gastroenterology Department, Key Laboratory for Precision Diagnosis and Treatment of Pediatric Digestive System Diseases, Shenzhen Children's Hospital, Shenzhen, 518036, China.; Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518052, China., Su L; Endoscopy Center and Gastroenterology Department, Key Laboratory for Precision Diagnosis and Treatment of Pediatric Digestive System Diseases, Shenzhen Children's Hospital, Shenzhen, 518036, China.; College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, 712100, China., Zeng Y; School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Gongchang Road, Shenzhen, Guangdong, 518107, China., Lin J; School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Gongchang Road, Shenzhen, Guangdong, 518107, China., Li W; Endoscopy Center and Gastroenterology Department, Key Laboratory for Precision Diagnosis and Treatment of Pediatric Digestive System Diseases, Shenzhen Children's Hospital, Shenzhen, 518036, China., Zou Y; Endoscopy Center and Gastroenterology Department, Key Laboratory for Precision Diagnosis and Treatment of Pediatric Digestive System Diseases, Shenzhen Children's Hospital, Shenzhen, 518036, China., Li S; Endoscopy Center and Gastroenterology Department, Key Laboratory for Precision Diagnosis and Treatment of Pediatric Digestive System Diseases, Shenzhen Children's Hospital, Shenzhen, 518036, China., Lin B; Endoscopy Center and Gastroenterology Department, Key Laboratory for Precision Diagnosis and Treatment of Pediatric Digestive System Diseases, Shenzhen Children's Hospital, Shenzhen, 518036, China., Li Z; Endoscopy Center and Gastroenterology Department, Key Laboratory for Precision Diagnosis and Treatment of Pediatric Digestive System Diseases, Shenzhen Children's Hospital, Shenzhen, 518036, China., Chen H; Endoscopy Center and Gastroenterology Department, Key Laboratory for Precision Diagnosis and Treatment of Pediatric Digestive System Diseases, Shenzhen Children's Hospital, Shenzhen, 518036, China., Huang Y; School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Gongchang Road, Shenzhen, Guangdong, 518107, China., Xu Q; College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, 712100, China., Chen H; School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Gongchang Road, Shenzhen, Guangdong, 518107, China. chenhb7@mail.sysu.edu.cn., Cheng F; School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Gongchang Road, Shenzhen, Guangdong, 518107, China. chengf9@mail.sysu.edu.cn., Dai D; Endoscopy Center and Gastroenterology Department, Key Laboratory for Precision Diagnosis and Treatment of Pediatric Digestive System Diseases, Shenzhen Children's Hospital, Shenzhen, 518036, China. daidong3529@sina.com.
Jazyk: angličtina
Zdroj: Journal of nanobiotechnology [J Nanobiotechnology] 2024 Oct 08; Vol. 22 (1), pp. 607. Date of Electronic Publication: 2024 Oct 08.
DOI: 10.1186/s12951-024-02856-z
Abstrakt: Ulcerative colitis (UC) belongs to chronic inflammatory disease with a relapsing characterization. Conventional oral drugs of UC are restricted in clinical by premature degradation in the gastrointestinal tract, modest efficacy, and adverse effects. CX5461 can treat autoimmune disease, immunological rejection, and vascular inflammation. However, low solubility, intravenous administration, and non-inflammatory targeting limited its clinical application. Herein, this work aims to develop Sophora Flavescens-derived exosomes-like nanovesicles carrying CX5461 (SFELNVs@CX5461) for efficient CX5461 oral delivery for UC therapy. We identified SFELNVs as nano-diameter (80 nm) with negative zeta potential (-32mV). Cellular uptake has shown that SFELNVs were targeted uptake by macrophages, thus increasing drug concentration. Additionally, oral SFELNVs@CX5461 exhibited good safety and stability, as well as inflammation-targeting ability in the gastrointestinal tract of dextran sodium sulfate (DSS)-induced colitis mice. In vivo, oral administration of SFELNVs and CX5461 could relieve mice colitis. More importantly, combined SFELNVs and CX5461 alleviated mice colitis by inhibiting pro-inflammatory factors (TNF-α, IL-1β, and IL-6) expression and promoting M2 macrophage polarization. Furthermore, SFELNVs promoted M2 polarization by miR4371c using miRNA sequencing. Our results suggest that SFELNVs@CX5461 represents a novel orally therapeutic drug that can ameliorate colitis, and a promising targeting strategy for safe UC therapy.
(© 2024. The Author(s).)
Databáze: MEDLINE
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