In vivo MR and Fluorescence Dual-modality Imaging of Atherosclerosis Characteristics in Mice Using Profilin-1 Targeted Magnetic Nanoparticles

Abstract

Aims: 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. Methods and 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. Conclusion: PC-NPs is a promising dual modality imaging probe, which may improve molecular diagnosis of plaque characteristics and evaluation of pharmaceutical interventions for atherosclerosis.

Emerging Strategies of Cancer Therapy Based on Ferroptosis

“…[42–44] Zanganeh et al showed an intrinsic therapeutic effect of ferumoxytol on the growth of early mammary cancers and lung cancer metastases in the liver and lungs. [45] In vitro , adenocarcinoma cells co-incubated with ferumoxytol and macrophages showed increased caspase-3 activity.…”

Optical Nanoparticles for Cardiovascular Imaging

“…Thus, imaging of the atherosclerotic lesion at this stage requires the use of targeted ONPs to either lipids or smooth muscle cells. This last possibility was the approach adopted by Wang et al In this case, the authors developed a fluorescent ONP by the appropiate combination of iron oxide nanoparticles with the Cy5.5 infrared dye. A schematic diagram of the multimodal (magnetic + fluorescent) ONP is shown in Figure a.…”

“…The ex vivo images of the carotid artery in three cases are also shown. Reproduced under the terms of the CC‐BY‐NC license . Copyright 2016, Ivyspring International Publisher.…”

Recent Advances in Managing Atherosclerosis via Nanomedicine

“…Inside the plaque, they observed elevated signals of the targeted NPs in the aortic root that are spatially different from the untargeted NPs. In 2016, Wang et al injected antibody‐conjugated iron oxide NPs into ApoE −/− mice to target profilin expressed by the smooth muscle cells, in order to image the plaques in the carotid artery. Contrary to the clinically proven therapeutic outcomes of using bio‐nanomaterials for cancer management, researchers are now assessing the potential of using bio‐nanomaterials in treating atherosclerosis or thrombotic complications, mostly at the preclinical level .…”