Abstract
BackgroundRupture of atherosclerotic plaque can cause acute malignant heart and cerebrovascular events, such as acute coronary heart disease, stroke and so on, which seriously threaten the safety of human life and property. Therefore, the early diagnosis and inhibition of atherosclerotic plaque progress still be a vital task.ResultsIn this study, we presented the development of composite mesoporous silica nanoparticle (Ru(bpy)3@SiO2-mSiO2, CMSN)-based nanomedicines (NMs) (Ru(bpy)3@SiO2-mSiO2@SRT1720@AntiCD36, CMSN@SRT@Anti) for accurate diagnosis and treatment of atherosclerosis (AS). In vitro cell experiments showed that both RAW264.7 and oxidized low density lipoprotein (ox-LDL)-stimulated RAW264.7 cells could significantly uptake CMSN@SRT@Anti. Conversely, little fluorescence signal could be observed in CMSN@SRT group, showing the excellent targeting ability of CMSN@SRT@Anti to Class II scavenger receptor, CD36 on macrophage. Additionally, such fluorescence signal was significantly stronger in ox-LDL-stimulated RAW264.7 cells, which might benefit from the upregulated expression of CD36 on macrophages after ox-LDL treatment. For another, compared with free SRT1720, CMSN@SRT@Anti had a better and more significant effect on the inhibition of macrophage foaming process, which indicated that drug-carrying mesoporous silicon with targeting ability could enhance the efficacy of SRT1720. Animal experimental results showed that after the abdominal injection of CMSN@SRT@Anti, the aortic lesions of ApoE-/-mice could be observed with obvious and persistent fluorescence signals. After 4 weeks post-treatment, the serum total cholesterol, aortic plaque status and area were significantly improved in the mouse, and the effect was better than that in the free SRT1720 group or the CMSN@SRT group.ConclusionsThe designed CMSN@SRT@Anti with excellent biocompatibility, high-performance and superior atherosclerosis-targeting ability has great potential for accurate identification and targeted therapy of atherosclerotic diseases.Graphic abstract
Highlights
Rupture of atherosclerotic plaque can cause acute malignant heart and cerebrovascular events, such as acute coronary heart disease, stroke and so on, which seriously threaten the safety of human life and property
Because the proliferation and migration of vascular smooth muscle cells (VSMCs) present in AS lesions is related to the formation of fibrous cap, profilin-1 highly expressed on the surface of VSMCs was chosen as the target [15]
Structure and characteristics of NMs The morphology of prepared Ru(bpy)3@SiO2 and CMSN were observed by Transmission Electron Microscopy (TEM)
Summary
Rupture of atherosclerotic plaque can cause acute malignant heart and cerebrovascular events, such as acute coronary heart disease, stroke and so on, which seriously threaten the safety of human life and property. The well designed NMs have been widely applied in various diseases such as the diagnosis and therapy of tumor, cardiovascular disease [4], the inhibition of bacterial infection [5, 6], bone regeneration [7] and so on. Macrophages phagocyte ox-LDL through scavenger receptors and transform into foam cells [12] Based on this mechanism, some diagnosis and therapy complex have been fabricated for AS. The transporter protein (TSPO) is significantly expressed on the surface of macrophages, and TSPO ligand iodine 125-DPA-713 prepared by Foss CA et al can efficiently accumulate in AS lesions, achieving the molecular diagnosis and treatment of AS with macrophages as the target [14]. Glinzer A et al prepared a near-infrared imaging agent Neutrophil Elastase 680 FAST to target elastic cell enzyme to realize the early diagnosis of AS [17]. Nearinfrared fluorescence imaging shows that AS plaques at the late stage in ApoE (−/−) mice could be noninvasively fluorescently imaged [18]
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