Molecularly Engineered Macrophage‐Derived Exosomes with Inflammation Tropism and Intrinsic Heme Biosynthesis for Atherosclerosis Treatment

作者：Guanghao Wu, Jinfeng Zhang, Qianru Zhao, Wan‐Ru Zhuang, Jingjing Ding, Chi Zhang, Haijun Gao, Dai‐Wen Pang, Kanyi Pu, Hai‐Yan Xie · 发表于：Angewandte Chemie International Edition · 年份：2019 · DOI：10.1002/anie.201913700 · 被引用次数：268 · 研究领域：Extracellular vesicles in disease、Inflammasome and immune disorders、Immune cells in cancer

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.