Molecular Imaging of Matrix Metalloproteinase-2 in Atherosclerosis Using a Smart Multifunctional PET/MRI Nanoparticle
文献类型：期刊论文
| 作者 | Tu, Yingfeng2,3,4; Ma, Xiaowei5; Chen, Hao3,4,6; Fan, Yuhua7; Jiang, Lei3,4; Zhang, Ruiping3,4,8,10; Cheng, Zhen1,3,4,6,9 |
| 刊名 | INTERNATIONAL JOURNAL OF NANOMEDICINE
 |
| 出版日期 | 2022 |
| 卷号 | 17页码:6773-6789 |
| 关键词 | atherosclerosis macrophage metalloproteinase-2 nanoparticles magnetic imaging positron tomography |
| ISSN号 | 1178-2013 |
| DOI | 10.2147/IJN.S385679 |
| 通讯作者 | Zhang, Ruiping(1900547207@qq.com) ; Cheng, Zhen(zcheng@simm.ac.cn) |
| 英文摘要 | Background: Matrix metalloproteinases from macrophages are important intraplaque components that play pivotal roles in plaque progression and regression. This study sought to develop a novel multifunctional positron emission tomography (PET) and magnetic resonance imaging (MRI) contrast agents based on MMP-2 cleavable nanoparticles to noninvasive assessment of MMP-2 activity in mouse carotid atherosclerotic plaques. Results: Macrophage-rich vascular lesions were induced by carotid ligation plus high-fat diet and streptozotocin-induced diabetes in CL57/BL6 mice. To render iron oxide nanoparticles (IONP) specific for the extracellular MMP-2, the magnetic nanoparticle base material has been derivatized with 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) for the nuclear tracer 64Cu labeling and the MMP-2-cleavable peptide modified with polyethylene glycol 2000, yielding a multi-modality reporter (64Cu-NOTA-IONP@MMP2c-PEG2K, MMP2cNPs) for PET/MR imaging. Small animal PET imaging and biodistribution data revealed that MMP2cNPs exhibited remarkable plaque uptake (3.06 +/- 0.87% ID/g and 1.83 +/- 0.28% ID/g at 4 and 12 h, respectively). And MMP2cNPs were rapidly cleared from the contralateral normal carotid artery, resulting in excellent plaque-to-normal carotid artery contrasts. Furthermore, in vivo MRI showed a preferential accumulation of MMP2cNPs in atherosclerotic lesions compared with the non-cleavable reference compound, MMP2ncNPs. In addition, histological analyses revealed iron accumulations in the carotid atherosclerotic plaque, in colocalization with MMP-2 expression and macrophages. Conclusion: Using a combination of innovative imaging modalities, in this study, we demonstrate the feasibility of applying the novel smart MMP2cNPs as a PET/MR hybrid imaging contrast agent for detection of MMP-2 in atherosclerotic plaque in vivo. |
| WOS关键词 | ACTIVATED MACROPHAGES ; PET-MR ; APOPTOSIS ; PLAQUE |
| 资助项目 | National Natural Science Foundation of China[81671746] ; National Natural Science Foundation of China[81827806] ; National Natural Science Foundation of China[81571747] ; National Natural Science Foundation of China[81771907] ; Office of Science (BER), US Department of Energy[DE-SC0008397] ; Postdoctoral Science Foundation of Heilongjiang Province[LBH-Q19037] ; Key research and development project of Shanxi Province[201703D321015-3] ; Science and technology innovation team project[201705D131026] ; Scientific and technological achievements transformation project of Shanxi Province[201704D131006] ; Shanxi Province Science Foundation[201701D221257] ; Shanxi Cancer Hospital[2017A01] |
| WOS研究方向 | Science & Technology - Other Topics ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000912780200001 |
| 出版者 | DOVE MEDICAL PRESS LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/303796]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Zhang, Ruiping; Cheng, Zhen |
| 作者单位 | 1.Stanford Univ, Canary Ctr Stanford Canc Early Detect, Biox Program, 1201 Welch Rd,Lucas Expans P095, Stanford, CA 94305 USA 2.Harbin Med Univ, Affiliated Hosp 1, Dept Cardiol, Harbin, Heilongjiang, Peoples R China 3.Stanford Univ, Dept Radiol, Mol Imaging Program Stanford, Stanford, CA USA 4.Stanford Univ, Biox Program, Stanford, CA USA 5.Cent South Univ, Xiangya Hosp 2, Dept Nucl Med, Changsha, Hunan, Peoples R China 6.Chinese Acad Sci, Shanghai Inst Mat Med, Mol Imaging Ctr, Shanghai, Peoples R China 7.Harbin Med Univ, Coll Pharm, Daqing, Heilongjiang, Peoples R China 8.Shanxi Acad Med Sci, Shanxi Med Univ, Hosp 3, Shanxi Bethune Hosp, Taiyuan, Peoples R China 9.Stanford Univ, Canary Ctr Stanford Canc Early Detect, Dept Radiol, Mol Imaging Program Stanford, 1201 Welch Rd,Lucas Expans P095, Stanford, CA 94305 USA 10.Shanxi Acad Med Sci, Shanxi Med Univ, Shanxi Bethune Hosp, Dept Radiol,Hosp 3, Taiyuan 030032, Peoples R China |
| 推荐引用方式 GB/T 7714 | Tu, Yingfeng,Ma, Xiaowei,Chen, Hao,et al. Molecular Imaging of Matrix Metalloproteinase-2 in Atherosclerosis Using a Smart Multifunctional PET/MRI Nanoparticle[J]. INTERNATIONAL JOURNAL OF NANOMEDICINE,2022,17:6773-6789. |
| APA | Tu, Yingfeng.,Ma, Xiaowei.,Chen, Hao.,Fan, Yuhua.,Jiang, Lei.,...&Cheng, Zhen.(2022).Molecular Imaging of Matrix Metalloproteinase-2 in Atherosclerosis Using a Smart Multifunctional PET/MRI Nanoparticle.INTERNATIONAL JOURNAL OF NANOMEDICINE,17,6773-6789. |
| MLA | Tu, Yingfeng,et al."Molecular Imaging of Matrix Metalloproteinase-2 in Atherosclerosis Using a Smart Multifunctional PET/MRI Nanoparticle".INTERNATIONAL JOURNAL OF NANOMEDICINE 17(2022):6773-6789. |
入库方式： OAI收割
来源：上海药物研究所
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