Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 36, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.nano.2021.102416
Keywords
Nanocluster; Chemokine receptor 2; Atherosclerosis; Positron emission tomography; Targeting
Funding
- National Institutes of Health [1R35HL145212, 1P01AI116501, R01HL153436, R01HL094601, R01HL151078]
- Veterans Administration Merit Review grant [1I01BX002730]
- Cystic Fibrosis Foundation
- Foundation for Barnes-Jewish Hospital
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This study validates CCR2 as a useful marker for atherosclerosis and suggests the potential of Cu-64-AuNC-ECLli as a targeted molecular imaging probe for future clinical translation.
The development of atherosclerosis therapy is hampered by the lack of molecular imaging tools to identify the relevant biomarkers and determine the dynamic variation in vivo. Here, we show that a chemokine receptor 2 (CCR2) targeted gold nanocluster conjugated with extracellular loop 1 inverso peptide (AuNC-ECL1i) determines the initiation, progression and regression of atherosclerosis in apolipoprotein E knock-out (ApoE(-/-)) mouse models. The CCR2 targeted Cu-64-AuNC-ECLli reveals sensitive detection of early atherosclerotic lesions and progression of plaques in ApoE(-/-) mice. CCR2 targeting specificity was confirmed by the competitive receptor blocking studies. In a mouse model of aortic arch transplantation, Cu-64-AuNC-ECLli accurately detects the regression of plaques. Human atherosclerotic tissues show high expression of CCR2 related to the status of the disease. This study confirms CCR2 as a useful marker for atherosclerosis and points to the potential of Cu-64-AuNC-ECLli as a targeted molecular imaging probe for future clinical translation. (C) 2021 Elsevier Inc. All rights reserved.
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