title: In vivo MR and Fluorescence Dual-modality Imaging of Atherosclerosis Characteristics in Mice Using Profilin-1 Targeted Magnetic Nanoparticles.
abstract: OBJECTIVE
  This study aims to explore non-invasive imaging of atherosclerotic plaque through magnetic resonance imaging (MRI) and near-infrared fluorescence (NIRF) by using profilin-1 targeted magnetic iron oxide nanoparticles (PF1-Cy5.5-DMSA-Fe3O4-NPs, denoted as PC-NPs) as multimodality molecular imaging probe in murine model of atherosclerosis.
  
  
  RESULTS
  PC-NPs were constructed by conjugating polyclonal profilin-1 antibody and NHS-Cy5.5 fluorescent dye to the surface of DMSA-Fe3O4-nanoparticles via condensation reaction. Murine atherosclerosis model was induced in apoE(-/-) mice by high fat and cholesterol diet (HFD) for 16 weeks. The plaque areas in aortic artery were detected with Oil Red O staining. Immunofluorescent staining and Western blot analysis were applied respectively to investigate profilin-1 expression. CCK-8 assay and transwell migration experiment were performed to detect vascular smooth muscle cells (VSMCs) proliferation. In vivo MRI and NIRF imaging of atherosclerotic plaque were carried out before and 36 h after intravenous injection of PC-NPs. Oil Red O staining showed that the plaque area was significantly increased in HFD group (p<0.05). Immunofluorescence staining revealed that profilin-1 protein was highly abundant within plaque in HFD group and co-localized with α-smooth muscle actin. Profilin-1 siRNA intervention could inhibit VSMCs proliferation and migration elicited by ox-LDL (p<0.05). In vivo MRI and NIRF imaging revealed that PC-NPs accumulated in atherosclerotic plaque of carotid artery. There was a good correlation between the signals of MRI and ex vivo fluorescence intensities of NIRF imaging in animals with PC-NPs injection.
  
  
  CONCLUSIONS
  PC-NPs is a promising dual modality imaging probe, which may improve molecular diagnosis of plaque characteristics and evaluation of pharmaceutical interventions for atherosclerosis.
authors.affiliation: 1. Department of Cardiology, Chinese PLA General Hospital, Beijing, 100853, China; 2. Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Shaanxi, 710032, China.
authors.forename: Yabin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 2. Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Shaanxi, 710032, China.
authors.forename: Jiangwei
authors.initials: J
authors.lastname: Chen
authors.affiliation: 1. Department of Cardiology, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: 2. Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Shaanxi, 710032, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Qiao
authors.affiliation: 1. Department of Cardiology, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Gao
authors.affiliation: 2. Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Shaanxi, 710032, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Su
authors.affiliation: 2. Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Shaanxi, 710032, China.
authors.forename: Sai
authors.initials: S
authors.lastname: Ma
authors.affiliation: 2. Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Shaanxi, 710032, China.
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Zhang
authors.affiliation: 2. Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Shaanxi, 710032, China.
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Li
authors.affiliation: 3. Center for Molecular Imaging and Translational Medicine, Xiamen University, Xiamen, 361005, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: 3. Center for Molecular Imaging and Translational Medicine, Xiamen University, Xiamen, 361005, China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Cao
authors.affiliation: 4. Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, MD 20892-2281, USA.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
authors.affiliation: 1. Department of Cardiology, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Yundai
authors.initials: Y
authors.lastname: Chen
authors.affiliation: 1. Department of Cardiology, Chinese PLA General Hospital, Beijing, 100853, China; 2. Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Shaanxi, 710032, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Cao
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000473:pathology*; D002232:Carbocyanines / Q000737:chemistry; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D005290:Ferric Compounds / Q000737:chemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D008297:Male; D051379:Mice; D064847:Multimodal Imaging / Q000379:methods*; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000502:physiology; D061848:Optical Imaging / Q000379:methods*; D051304:Profilins / Q000378:metabolism*; D011485:Protein Binding; D004113:Succimer / Q000737:chemistry
chemical_list: C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; D051304:Profilins; C000499:ferric oxide; D004113:Succimer
keywords: Atherosclerosis; DMSA-Fe3O4-nanoparticles; Molecular imaging; Profilin-1