Highly sensitive magnetic particle imaging of vulnerable atherosclerotic plaque with active myeloperoxidase-targeted nanoparticles
Tong, Wei2,3,4; Hui, Hui4,5; Shang, Wenting4,5; Zhang, Yingqian3; Tian, Feng3; Ma, Qiang3; Yang, Xin4,5; Tian, Jie1,4,5; Chen, Yundai2,3
刊名THERANOSTICS
2021
卷号11期号:2页码:506-521
关键词myeloperoxidase vulnerable plaque magnetic particle imaging fluorescence imaging computed tomographic angiography
ISSN号1838-7640
DOI10.7150/thno.49812
通讯作者Hui, Hui(hui.hui@ia.ac.cn) ; Tian, Jie(jie.tian@ia.ac.cn) ; Chen, Yundai(cyundai@vip.163.com)
英文摘要Inflammation is a pivotal driver of atherosclerotic plaque progression and rupture and is a target for identifying vulnerable plaques. However, challenges arise with the current in vivo imaging modalities for differentiating vulnerable atherosclerotic plaques from stable plaques due to their low specificity and sensitivity. Herein, we aimed to develop a novel multimodal imaging platform that specifically targets and identifies high-risk plaques in vivo by detecting active myeloperoxidase (MPO), a potential inflammatory marker of vulnerable atherosclerotic plaque. Methods: A novel multimodal imaging agent, 5-HT-Fe3O4-Cy7 nanoparticles (5HFeC NPs), used for active MPO targeting, was designed by conjugating superparamagnetic iron oxide nanoparticles (SPIONs) with 5-hydroxytryptamine and cyanine 7 N-hydroxysuccinimide ester. The specificity and sensitivity of 5HFeC NPs were evaluated using magnetic particle imaging (MPI), fluorescence imaging (FLI), and computed tomographic angiography (CTA) in an ApoE(-/-) atherosclerosis mouse model. Treatment with 4-ABAH, an MPO inhibitor, was used to assess the monitoring ability of 5HFeC NPs. Results: 5HFeC NPs can sensitively differentiate and accurately localize vulnerable atherosclerotic plaques in ApoE(-/-) mice via MPI/FLI/CTA. High MPI and FLI signals were observed in atherosclerotic plaques within the abdominal aorta, which were histologically confirmed by multiple high-risk features of macrophage infiltration, neovascularization, and microcalcification. Inhibition of active MPO reduced accumulation of 5HFeC NPs in the abdominal aorta. Accumulation of 5HFeC NPs in plaques enabled quantitative evaluation of the severity of inflammation and monitoring of MPO activity. Conclusions: This multimodal MPI approach revealed that active MPO-targeted nanoparticles might serve as a method for detecting vulnerable atherosclerotic plaques and monitoring MPO activity.
资助项目National Key Research and Development Program of China[2017YFA0700401] ; National Key Research and Development Program of China[2016YFC0103803] ; National Key Research and Development Program of China[2017YFA0205200] ; National Natural Science Foundation of China[81671851] ; National Natural Science Foundation of China[81827808] ; National Natural Science Foundation of China[81870178] ; National Natural Science Foundation of China[81527805] ; National Natural Science Foundation of China[81971680] ; National Natural Science Foundation of China[81800221] ; National Natural Science Foundation of China[81671731] ; National Natural Science Foundation of China[81227901] ; CAS Strategic Priority Research Program[XDB32030200] ; Youth Innovation Promotion Association[2018167] ; CAS Scientific Instrument R&D Program of the Chinese Academy of Sciences[YJKYYQ20170075]
WOS关键词ACUTE CORONARY SYNDROMES ; ARTERY-DISEASE ; RISK ; INFLAMMATION ; IDENTIFICATION ; FERUMOXYTOL ; PROGRESSION ; MECHANISMS ; STABILITY ; TRACERS
WOS研究方向Research & Experimental Medicine
语种英语
出版者IVYSPRING INT PUBL
WOS记录号WOS:000585989200003
资助机构National Key Research and Development Program of China ; National Natural Science Foundation of China ; CAS Strategic Priority Research Program ; Youth Innovation Promotion Association ; CAS Scientific Instrument R&D Program of the Chinese Academy of Sciences
内容类型期刊论文
源URL[http://ir.ia.ac.cn/handle/173211/41760]  
专题自动化研究所_中国科学院分子影像重点实验室
通讯作者Hui, Hui; Tian, Jie; Chen, Yundai
作者单位1.Beihang Univ, Beijing Adv Innovat Ctr Big Data Based Precis Med, Sch Med, Beijing 100083, Peoples R China
2.Chinese Peoples Liberat Army Gen Hosp, Med Sch Chinese PLA, Beijing 100853, Peoples R China
3.Chinese Peoples Liberat Army Gen Hosp, Med Ctr 6, Dept Cardiol, Beijing 100853, Peoples R China
4.Chinese Acad Sci, Inst Automat, CAS Key Lab Mol Imaging, Beijing 100190, Peoples R China
5.Univ Chinese Acad Sci, Beijing, Peoples R China
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Tong, Wei,Hui, Hui,Shang, Wenting,et al. Highly sensitive magnetic particle imaging of vulnerable atherosclerotic plaque with active myeloperoxidase-targeted nanoparticles[J]. THERANOSTICS,2021,11(2):506-521.
APA Tong, Wei.,Hui, Hui.,Shang, Wenting.,Zhang, Yingqian.,Tian, Feng.,...&Chen, Yundai.(2021).Highly sensitive magnetic particle imaging of vulnerable atherosclerotic plaque with active myeloperoxidase-targeted nanoparticles.THERANOSTICS,11(2),506-521.
MLA Tong, Wei,et al."Highly sensitive magnetic particle imaging of vulnerable atherosclerotic plaque with active myeloperoxidase-targeted nanoparticles".THERANOSTICS 11.2(2021):506-521.
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