Size-dependent macrophage-targeting of mannose-modified rosiglitazone liposomes to alleviate inflammatory bowel disease

作     者：Erjin Wang Run Han Mingyue Wu Yuan He Yaxin Cheng Jiahong Lu Ying Zheng Erjin Wang;Run Han;Mingyue Wu;Yuan He;Yaxin Cheng;Jiahong Lu;Ying Zheng

作者机构：State Key Laboratory of Quality Research in Chinese MedicineInstitute of Chinese Medical Sciences(ICMS)University of MacaoMacao 999078China Department of PharmacyXuzhou Medical UniversityXuzhou 221004China Faculty of Health SciencesUniversity of MacaoMacao 999078China Guangdong-Hong Kong-Macao Joint Lab on Chinese Medicine and Immune Disease ResearchUniversity of MacaoMacao 999078China 

出 版 物：《Chinese Chemical Letters》 (中国化学快报（英文版）)

年 卷 期：2024年第35卷第1期

页      面：385-391页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：the Macao Science and Technology Development Fund(No.0086/2021/A2) Shenzhen Fundamental Research Program(No.SGDX20210823103804030) the 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund(Guangdong-Hong Kong-Macao Joint Lab,No.2020B1212030006) Guangdong Basic and Applied Basic Research Foundation(No.2022A1515012416) 

主　　题：Macrophage targeting Liposome Mannose Particle size Inflammatory bowel disease 

摘      要：Inflammatory bowel disease (IBD) is a refractory chronic intestinal inflammatory disease caused by a malfunction of immune system. As the key immune cells in the intestine, macrophages play an important role in maintaining intestinal homeostasis and tissue repair of the IBD. Pharmacological modulation of macrophage function exhibits the promising therapeutic effect for IBD. In this study, mannose-modified liposomes (MAN-LPs) are prepared for macrophage targeting to improve therapeutic efficiency. Rosiglitazone (ROSI) as an agonist of peroxisome proliferators-activated receptor γ (PPAR-γ) is used as the model drug to fabricate different sized liposomes. The impacts of mannose modification and particle size for macrophage targeting are investigated in cells, zebrafish, and mouse models and the therapeutic effects of the MAN-LPs are evaluated on dextran sulfate sodium (DSS)-induced IBD mouse. Compared to unmodified liposome, MAN-LPs display higher uptake by RAW 264.7 cells and better co-localization with macrophage in zebrafish model. Furthermore, MAN-LPs could effectively accumulate in the inflammatory intestinal sites in IBD mouse model. Most importantly, the targeting ability of MAN-LPs is obviously enhanced with the increasing of particle size, whereas the largest MAN-LPs particles achieve the best anti-inflammatory effect in cells, and a higher therapeutic efficiency in IBD mouse model. Therefore, mannose-modified liposome is a promising strategy for macrophage-targeting in IBD treatment. Particle size of MAN-LPs will affect macrophage targeting ability, as well as the therapeutic effect in-vivo.