Macrophage-mannose-receptor-targeted photoactivatable agent for in vivo imaging and treatment of atherosclerosis

• Published in: International journal of pharmaceutics 2024-04, Vol.654, p.123951-123951, Article 123951
• Main 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
• Format: Article
• Language: English
• Subjects: Animals; Atherosclerosis; Atherosclerosis - diagnostic imaging; Atherosclerosis - drug therapy; Cell Line, Tumor; Chlorin e6; Humans; Macrophage; Macrophages; Mannose; Mice; Nanoparticles - chemistry; Photochemotherapy - methods; Photodynamic therapy; Photosensitiser; Photosensitizing Agents - chemistry; Photosensitizing Agents - pharmacology; Polyethylene Glycols - chemistry; Porphyrins - chemistry; Theranostics
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2024.123951

[Display omitted] •Novel targeted theranostic system MAN-PEG-Ce6 was developed.•Targeted MAN-PEG-Ce6 internalized in foam cell through mannose receptor-mediated endocytosis.•Theranostic MAN-PEG-Ce6 emitted fluorescence and induced apoptosis with light illumination.•MAN-PEG-Ce6 was accumulated in plaques by targeting mannose receptor-positive macrophages.•Photoactivation of MAN-PEG-Ce6 reduced plaque inflammation in advanced atheroma at 1 week.•Phototheransotic agent MAN-PEG-Ce6 had negligible toxicity in vivo. 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.