Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 19, Issue -, Pages 81-94Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2019.04.003
Keywords
Atherosclerosis; Macrophages; SR-AI; Molecular imaging; Ultrasmall gold nanoclusters
Funding
- National Natural Science Foundation of China [81701826]
- Key Program of Natural Science Foundation of Tianjin [16KPXMSF00140, 16JCZDJC35100]
- Key Program of the Tianjin Health and Family Planning Commission [16KG115, 15KG137]
- Youth Science Foundation of the Second Hospital Center Laboratory of Tianjin Medical University [2017YDEY11]
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Owing to the high morbidity and mortality of cardiovascular diseases resulting from atherosclerosis, developing specific noninvasive diagnostic methods to distinguish vulnerable atherosclerotic plaques becomes urgent and mandatory. Herein, scavenger receptors AI (SR-AI), a secreted biomarker associated with foam macrophages, was selected as a target for identifying vulnerable plaques. A dual-modality imaging probe (PP1-Au@GSH@Gd NCs) was constructed by covalently attaching a peptidic SR-AI ligand, PP1 to gadolinium-integrated gold nanoclusters, which exhibited remarkably improved fluorescence signal and longitudinal relaxivity with highly loaded Au and Gd species. In vitro cellular binding studies showed preferential affinity of PP1-Au@GSH@Gd NCs to activated macrophages in SR-AI-dependent manner. In vivo MR/fluorescence images presented robust and prolonged plaque contrast enhancement in established ApoE(-/-) mice models thanks to favorable targeting efficacy of PP1-Au@GSH@Gd NCs. Collectively, the noninvasive MR/fluorescence molecular imaging strategy with PP1-Au@GSH@Gd NCs holds great promise for precise clinical diagnosis of vulnerable plaques. (C) 2019 Elsevier Inc. All rights reserved.
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