单核细胞模拟造影剂使动脉粥样硬化病变的磁共振成像具有针对性和敏感性。

IF 9.6 2区 医学 Q1 ENGINEERING, BIOMEDICAL
Joshua Rousseau, Ting-Yun Wang, Samantha McClendon, Dakota Ortega, Mark Orlando, Scott C Beeman, Benjamin B Bartelle, Kuei-Chun Wang
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引用次数: 0

摘要

超顺磁性氧化铁纳米颗粒(SPION)作为动脉粥样硬化磁共振成像(MRI)的T2造影剂进行了研究。然而,它们的非特异性生物分布和低斑块位点生物利用度限制了它们的转化潜力。为了解决这些挑战,单核细胞膜覆盖的聚合纳米颗粒包裹SPION (MoNP-SPION),以增强斑块特异性积累。物理化学表征证实了MoNP-SPION配方的成功,其水动力尺寸为≈271 nm, SPION负载效率为8.5%,r2弛度为397.7 mM-1 s-1。体外实验和幻影成像表明,与其成分相比,MoNP-SPION对tnf α活化的内皮细胞具有显著增强的靶向效率,同时最大限度地减少了单核细胞和巨噬细胞的摄取。T2*加权离体MRI证实MoNP-SPION在动脉粥样硬化区优先积聚,同时保留血管无病变区域。动脉粥样硬化小鼠的体内MRI显示,MoNP-SPION,而非未包被的SPION或游离SPION,在颈动脉分叉和主动脉根(斑块发育明显的区域)诱导强烈的T2*加权信号降低,证实了其增强动脉粥样硬化成像的能力。此外,毒性评估证实了MoNP-SPION的生物相容性。总之,研究结果突出了MoNP-SPION作为一种有前途的仿生造影剂,可以改善基于mri的动脉粥样硬化诊断,在监测斑块进展和治疗结果方面具有潜在的应用前景。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Monocyte-Mimetic Contrast Agent Enables Targeted and Sensitive Magnetic Resonance Imaging of Atherosclerotic Lesions.

Superparamagnetic iron oxide nanoparticles (SPION) are investigated as T2 contrast agents for magnetic resonance imaging (MRI) of atherosclerosis. However, their nonspecific biodistribution and low plaque-site bioavailability limit their translational potential. To address these challenges, monocyte membrane-cloaked polymeric nanoparticles encapsulating SPION (MoNP-SPION) to enhance plaque-specific accumulation is developed. Physicochemical characterization confirmed successful MoNP-SPION formulation, with a hydrodynamic size of ≈271 nm, SPION loading efficiency of 8.5%, and r2 relaxivity of 397.7 mM-1 s-1. In vitro assays and phantom imaging demonstrated that MoNP-SPION exhibited significantly enhanced targeting efficiency toward TNFα-activated endothelial cells while minimizing uptake by monocytes and macrophages compared to its constituents. T2*-weighted ex vivo MRI confirmed the preferential accumulation of MoNP-SPION in atheroprone regions while sparing lesion-free areas of the vasculature. In vivo MRI of atherosclerotic mice revealed that MoNP-SPION, but not the uncoated counterpart or free SPION, induced strong T2*-weighted signal reductions at the carotid bifurcations and aortic root, areas with significant plaque development, confirming its ability to enhance atherosclerosis imaging. Furthermore, toxicity assessments demonstrated the biocompatibility of MoNP-SPION. Together, the findings highlight MoNP-SPION as a promising biomimetic contrast agent for improving MRI-based diagnosis of atherosclerosis, with potential applications in monitoring plaque progression and treatment outcomes.

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来源期刊
Advanced Healthcare Materials
Advanced Healthcare Materials 工程技术-生物材料
CiteScore
14.40
自引率
3.00%
发文量
600
审稿时长
1.8 months
期刊介绍: Advanced Healthcare Materials, a distinguished member of the esteemed Advanced portfolio, has been dedicated to disseminating cutting-edge research on materials, devices, and technologies for enhancing human well-being for over ten years. As a comprehensive journal, it encompasses a wide range of disciplines such as biomaterials, biointerfaces, nanomedicine and nanotechnology, tissue engineering, and regenerative medicine.
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