Macrophage-mannose-receptor-targeted photoactivatable agent for in vivo imaging and treatment of atherosclerosis
- Authors
- Lee, Seung-Yul; Kim, Jin Hyuk; Song, Joon Woo; Min, Ji Seon; Kim, Hyun Jung; Kim, Ryeong Hyun; Ahn, Jae Won; Yoo, Hongki; Park, Kyeongsoon; Kim, Jin Won
- Issue Date
- Apr-2024
- Publisher
- Elsevier B.V.
- Keywords
- Atherosclerosis; Chlorin e6; Macrophage; Photodynamic therapy; Photosensitiser; Theranostics
- Citation
- International Journal of Pharmaceutics, v.654
- Journal Title
- International Journal of Pharmaceutics
- Volume
- 654
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/73007
- DOI
- 10.1016/j.ijpharm.2024.123951
- ISSN
- 0378-5173
1873-3476
- Abstract
- Previous studies have demonstrated the effects of theranostic agents on atherosclerotic plaques. However, there is limited information on targeted theranostics for photodynamic treatment of atherosclerosis. This study aimed to develop a macrophage-mannose-receptor-targeted photoactivatable nanoagent that regulates atherosclerosis and to evaluate its efficacy as well as safety in atherosclerotic mice. We synthesised and characterised D-mannosamine (MAN)-polyethylene glycol (PEG)-chlorin e6 (Ce6) for phototheranostic treatment of atherosclerosis. The diagnostic and therapeutic effects of MAN-PEG-Ce6 were investigated using the atherosclerotic mouse model. The hydrophobic Ce6 photosensitiser was surrounded by the hydrophilic MAN-PEG outer shell of the self-assembled nanostructure under aqueous conditions. The MAN-PEG-Ce6 was specifically internalised in macrophage-derived foam cells through receptor-mediated endocytosis. After laser irradiation, the MAN-PEG-Ce6 markedly increased singlet oxygen generation. Intravital imaging and immunohistochemistry analyses verified MAN-PEG-Ce6′s specificity to plaque macrophages and its notable anti-inflammatory impact by effectively reducing mannose-receptor-positive macrophages. The toxicity assay showed that MAN-PEG-Ce6 had negligible effects on the biochemical profile and structural damage in the skin and organs. Targeted photoactivation with MAN-PEG-Ce6 thus has the potential to rapidly reduce macrophage-derived inflammatory responses in atheroma and present favourable toxicity profiles, making it a promising approach for both imaging and treatment of atherosclerosis. © 2024
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