한빛사논문
- 조회252
Jin Hyuk Kim #,1,2, Joon Woo Song #,2, Yeon Hoon Kim #,3, Hyun Jung Kim 2, Ryeong Hyun Kim 2, Ye Hee Park 2, Hyeong Soo Nam 3, Dong Oh Kang 2, Hongki Yoo 3, Kyeongsoon Park 4, Jin Won Kim 1,2
1BK21 Graduate Program, Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Korea (J.H.K., J.W.K.).
2Multimodal Imaging and Theranostic Laboratory, Cardiovascular Center, Korea University Guro Hospital (J.H.K., J.W.S., H.J.K., R.H.K., Y.H.P., D.O.K., J.W.K.).
3Department of Mechanical Engineering, KAIST, Korea (Y.H.K., H.S.N., H.Y.).
4Department of Systems Biotechnology, Chung-Ang University, Anseong, Gyeonggi, Korea (K.P.).
#Contributed equally.
Correspondence to: Jin Won Kim, MD, PhD, Kyeongsoon Park, PhD, Hongki Yoo, PhD
Abstract
BACKGROUND: Atherosclerosis is a chronic inflammatory disease causing a fatal plaque rupture, and its key aspect is a failure to resolve inflammation. We hypothesize that macrophage-targeted near-infrared fluorescence emitting photoactivation could simultaneously assess macrophage/lipid-rich plaques in vivo and facilitate inflammation resolution.
METHODS: We fabricated a Dectin-1–targeted photoactivatable theranostic agent through the chemical conjugation of the near-infrared fluorescence–emitting photosensitizer chlorin e6 and the Dectin-1 ligand laminarin (laminarin-chlorin e6 [LAM-Ce6]). Intravascular photoactivation by a customized fiber-based diffuser after administration of LAM-Ce6 effectively reduced inflammation in the targeted plaques of atherosclerotic rabbits in vivo as serially assessed by dual-modal optical coherence tomography-near-infrared fluorescence structural-molecular catheter imaging after 4 weeks.
RESULTS: The number of apoptotic macrophages peaked at 1 day after laser irradiation and then resolved until 4 weeks. Autophagy was strongly augmented 1 hour after the light therapy, with the formation of autophagolysosomes. LAM-Ce6 photoactivation increased the terminal deoxynucleotidyl transferase dUTP (deoxyuridine triphosphate) nick end labeling/RAM11 (rabbit monocyte/macrophage antibody)- and MerTK (c-Mer tyrosine kinase)-positive cells in the plaques, suggesting enhanced efferocytosis. In line with inflammation resolution, photoactivation reduced the plaque burden through fibrotic replacement via the TGF (transforming growth factor)-β/CTGF (connective tissue growth factor) pathway.
CONCLUSIONS: Optical coherence tomography-near-infrared fluorescence imaging-guided macrophage Dectin-1–targetable photoactivation could induce the transition of macrophage/lipid-rich plaques into collagen-rich lesions through autophagy-mediated inflammation resolution and TGF-β–dependent fibrotic replacement. This novel strategy offers a new opportunity for the catheter-based theranostic strategy.
논문정보
- Research article
- 2024년 07월 (BRIC 등록일 2024-08-07)
- 국내 연구진
- 바이오·의료융합 > 바이오센싱 및 나노바이오물질
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