Molecularly Engineered Macrophage-Derived Exosomes with Inflammation Tropism and Intrinsic Heme Biosynthesis for Atherosclerosis Treatment
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.
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Molecularly engineered M2 macrophage-derived exosomes may contribute to treating atherosclerosis by suppressing inflammation via chemokine receptors and inflammation inhibitory cytokines secreted by M2 macrophages.
“Wu et al. reported that molecularly engineered M2 macrophage-derived exosomes may contribute to treating atherosclerosis by suppressing inflammation via chemokine receptors and inflammation inhibitory cytokines secreted by M2 macrophages.”
From The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System (2022) · cites this paper as [95]
Encapsulated hexyl 5-aminolevulinate hydrochloride can diminish inflammation effectively by intrinsic biosynthesis and metabolism of heme.
“Meanwhile, the encapsulated hexyl 5-aminolevulinate hydrochloride can diminish inflammation effectively by intrinsic biosynthesis and metabolism of heme [95].”
From The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System (2022) · cites this paper as [95]
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- Authors
- Wu, G., Zhang, J., Zhao, Q., Zhuang, W., Ding, J., Zhang, C., Gao, H., Pang, D., Pu, K., & Xie, H.
- Affiliations
- Beijing Institute of Technology (CN)
- School of Life Science Beijing Institute of Technology No. 5 South Zhong Guan Cun Street Beijing 100081 China
- Nanyang Technological University (SG)
- Nankai University (CN)
- Corresponding author
- Pu, Kanyi
- Xie, Hai‐Yan
- ORCID
- Venue
- Angewandte Chemie International Edition
- Publisher
- Wiley
- Published
- 2020-01-23
- Volume
- 59
- Issue
- 10
- Pages
- 4068-4074
- ISSN
- 1433-7851 (ISSN-L)
- 1521-3773
- OpenAlex
- W2995916615
- Semantic Scholar
- 1b2c883b13774f8c9c8716a9cad9478d68fa7697
- Cited by
- 269
- References
- 60
- Citations by year
- 2026: 22 · 2025: 47 · 2024: 44 · 2023: 45 · 2022: 56 · 2021: 41 · 2020: 14
- FWCI
- 9.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Angewandte Chemie International Edition (publishedVersion)
- PubMed (publishedVersion)
- DR-NTU (Nanyang Technological University) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Keywords
- atherosclerosis, macrophage-derived exosomes, M2 macrophages, heme biosynthesis, carbon monoxide, bilirubin, protoporphyrin IX, 5-aminolevulinic acid, electroporation, chemokine receptor targeting, anti-inflammatory therapy, fluorescence imaging
- MeSH terms
- Animals, Anti-Inflammatory Agents, Non-Steroidal, Heme, Inflammation, Macrophages, Male, Mice, Inbred BALB C, Mice, Knockout, Tropism, Atherosclerosis, Mice, Exosomes
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