靶向动脉粥样硬化携全氟己烷纳米粒的MRI/荧光显像及对活化巨噬细胞的影响

Magnetic Resonance/Fluorescence Imaging of Perfluorohexane Loaded Nanoparticles Targeting Atherosclerosis and Its Eff onActivatedMacrophages

目的 制备一种载相变材料全氟己烷(perfluorohexane, PFH)和配体硫酸葡聚糖(dextran sulfate, DS)的靶向清道夫受体A的磁共振成像(magnetic resonance imaging, MRI)/近红外荧光双模态分子探针,研究其对活化巨噬细胞的影响。方法 采用双乳化法和静电吸附法制备纳米粒(PFH-Fe/DiR-DS),检测该纳米粒的理化性质,研究其体外MRI和近红外荧光成像情况及其相变性能,分析纳米粒对活化巨噬细胞的靶向性和相变诱导巨噬细胞凋亡的情况。结果 制备的PFH-Fe/DiR-DS纳米粒的最终尺寸为269~303 nm,分散性好,具有壳核结构,表面呈光滑的三维球形。纳米粒具有良好的MRI和近红外荧光多模态成像能力,在低强度聚焦超声(low-intensity focused ultrasound, LIFU)的辐照下能够发生相变。纳米粒对活化的巨噬细胞具有较高的亲和力,被巨噬细胞内吞后在LIFU的辐照下,能够通过声致相变效应诱导巨噬细胞凋亡。结论 本研究成功构建了靶向动脉粥样硬化(atherosclerosis, AS)斑块的多模态多功能PFH-Fe/DiR-DS纳米粒,在LIFU辐照下诱导巨噬细胞凋亡,应用MRI和近红外荧光分子显像技术监控评估斑块状况,有望能够对AS斑块进行特异性诊断和靶向治疗。

Objective To prepare a magnetic resonance imaging(MRID)/near-infrared fluorescence bimodal molecular probe targeting scavenger receptor A,which is loaded with a phase change material perfluorohexane(PFH)and dextran sulfate(DS),and to study its effects on activated macrophage.Methods Nanoparticles(PFH-Fe/DiR-DS)were prepared by double emulsion method and electrostatic adsorption method,and their physical and chemical properties were detected,the MRI and near-infrared fluorescence imaging in vitro and its phase change performance were studied,and the targeting of nanoparticles to activated macrophages and the apoptosis of macrophages induced by phase change were analyzed.Results The final size of the prepared PFH-Fe/DiR-DS nanoparticles was 269-303 nm,with good dispersion,shell structure and smooth three-dimensional spherical surface.Nanoparticles had good MRI and capabilities of near-infrared fluorescence multimodal imaging,and could undergo phase transformation under the irradiation of low-intensity focused ultrasound(LIFU).The nanoparticles had a high affinity for activated macrophages,and after endocytosis of macrophages under LIFU irradiation,they could induce apoptosis of macrophages through the sonogenic phase transition effect.Conclusion In this study,multimodal and multifunctional PFH-Fe/DiR-DS nanoparticles targeting atherosclerotic(AS)plaques is successfully constructed,and macrophage apoptosis is induced under LIFU irradiation.The application of MRI and near-infrared fluorescence molecular imaging technology to monitor and evaluate the status of plaque is expected to be able to carry out specific diagnosis and targeted treatment of AS plaque.