Molecularly Engineered Macrophage‐Derived Exosomes with Inflammation Tropism and Intrinsic Heme Biosynthesis for Atherosclerosis Treatment. Issue 10 (23rd January 2020)

• Record Type: Journal Article
• Authors: Wu, Guanghao; Zhang, Jinfeng; Zhao, Qianru; Zhuang, Wanru; Ding, Jingjing; Zhang, Chi; Gao, Haijun; Pang, Dai‐Wen; Pu, Kanyi; Xie, Hai‐Yan
• Is Part Of: Angewandte Chemie international edition. Volume 59:Issue 10(2020)
• Page Start: 4068
• Page End: 4074
• Publication Date: 2020-01-23
• Subjects: biosynthesis -- exosomes -- inflammation -- membrane proteins; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201913700
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Atherosclerosis (AS) is a major contributor to cardiovascular diseases worldwide, and alleviating inflammation is a promising strategy for AS treatment. Here, we report molecularly engineered M2 macrophage‐derived exosomes (M2 Exo) with inflammation‐tropism and anti‐inflammatory capabilities for AS imaging and therapy. M2 Exo are derived from M2 macrophages and further electroporated with FDA‐approved hexyl 5‐aminolevulinate hydrochloride (HAL). After systematic administration, the engineered M2 Exo exhibit excellent inflammation‐tropism and anti‐inflammation effects via the surface‐bonded chemokine receptors and the anti‐inflammatory cytokines released from the anti‐inflammatory M2 macrophages. Moreover, the encapsulated HAL can undergo intrinsic biosynthesis and metabolism of heme to generate anti‐inflammatory carbon monoxide and bilirubin, which further enhance the anti‐inflammation effects and finally alleviate AS. Meanwhile, the intermediate protoporphyrin IX (PpIX) of the heme biosynthesis pathway permits the fluorescence imaging and tracking of AS. Abstract : M2 macrophage‐derived exosomes molecularly engineered with the drug hexyl 5‐aminolevulinate hydrochloride (HAL) can actively target and transmigrate to atherosclerotic lesions, wherein the biosynthesis and metabolism of heme induced by HAL produces CO and bilirubin. This, along with the anti‐inflammatory cytokines in exosomes, acts to significantly alleviate atherosclerosis.