Molecularly engineered macrophage-derived exosomes with inflammation tropism and intrinsic heme biosynthesis for atherosclerosis treatment

• Main Authors: Wu, Guanghao, Zhang, Jinfeng, Zhao, Qianru, Zhuang, Wanru, Ding, Jingjing, Zhang, Chi, Gao, Haijun, Pang, Dai-Wen, Pu, Kanyi, Xie, Hai-Yan
• Other Authors: School of Chemical and Biomedical Engineering
• Format: Article
• Language: English
• Published: 2022
• Subjects: Engineering::Chemical engineering; Biosynthesis; Exosomes
• Online Access: https://hdl.handle.net/10356/162027
• Institution: Nanyang Technological University

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.