Wu Guanghao, Zhang Jinfeng, Zhao Qianru, Zhuang Wanru, Ding Jingjing, Zhang Chi, Gao Haijun, Pang Dai-Wen, Pu Kanyi, Xie Hai-Yan
School of Life Science, Beijing Institute of Technology, No. 5 South Zhong Guan Cun Street, Beijing, 100081, China.
School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore, 637457, Singapore.
Angew Chem Int Ed Engl. 2020 Mar 2;59(10):4068-4074. doi: 10.1002/anie.201913700. Epub 2020 Jan 23.
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.
动脉粥样硬化（AS）是全球心血管疾病的主要成因，减轻炎症是治疗AS的一种有前景的策略。在此，我们报告了具有炎症靶向性和抗炎能力的分子工程化M2巨噬细胞衍生外泌体（M2 Exo），用于AS成像和治疗。M2 Exo源自M2巨噬细胞，并进一步用美国食品药品监督管理局（FDA）批准的盐酸己基5-氨基乙酰丙酸（HAL）进行电穿孔处理。经系统给药后，工程化的M2 Exo通过表面结合的趋化因子受体以及抗炎M2巨噬细胞释放的抗炎细胞因子，表现出优异的炎症靶向性和抗炎作用。此外，封装的HAL可进行血红素的内在生物合成和代谢，以生成抗炎一氧化碳和胆红素，这进一步增强了抗炎作用并最终减轻AS。同时，血红素生物合成途径的中间产物原卟啉IX（PpIX）允许对AS进行荧光成像和追踪。
