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载脂蛋白 E 基因敲除小鼠动脉粥样硬化斑块的多模态分子成像研究

Multimodal molecular imaging of atherosclerosis: Nanoparticles functionalized with scFv fragments of an anti-αIIbβ3 antibody.

机构信息

Centre de Résonance Magnétiques des Systèmes Biologiques, Bordeaux, France..

CNRS, Univ. Bordeaux, Bordeaux INP, Pessac, France..

出版信息

Nanomedicine. 2019 Nov;22:102082. doi: 10.1016/j.nano.2019.102082. Epub 2019 Aug 9.

Abstract

Due to the wealth of actors involved in the development of atherosclerosis, molecular imaging based on the targeting of specific markers would substantiate the diagnosis of life-threatening atheroma plaques. To this end, TEG4 antibody is a promising candidate targeting the activated platelets (integrin αIIbβ3) highly represented within the plaque. In this study, scFv antibody fragments were used to functionalize multimodal imaging nanoparticles. This grafting was performed in a regio-selective way to preserve TEG4 activity and the avidity of the nanoparticles was studied with respect to the number of grafted antibodies. Subsequently, taking advantage of the nanoparticle bimodality, both near infrared fluorescence and magnetic resonance imaging of the atheroma plaque were performed in the ApoE mouse model. Here we describe the design of the targeted nanoparticles, and a quantification method for their detection in mice, both ex vivo and in vivo, highlighting their value as a potential diagnosis agent.

摘要

由于动脉粥样硬化的发展涉及到大量的因素,因此基于特定标志物靶向的分子成像将为危及生命的动脉粥样斑块的诊断提供依据。为此,TEG4 抗体是一种很有前途的针对活化血小板(整合素 αIIbβ3)的候选物,而活化血小板在斑块中高度表达。在这项研究中,scFv 抗体片段被用于功能化多模态成像纳米颗粒。这种接枝是通过区域选择性的方式进行的,以保持 TEG4 的活性,并研究了纳米颗粒的亲和性与接枝抗体的数量有关。随后,利用纳米颗粒的双重模态特性,在 ApoE 小鼠模型中进行了动脉粥样硬化斑块的近红外荧光和磁共振成像。在这里,我们描述了靶向纳米颗粒的设计,并描述了一种在体外和体内定量检测它们的方法,突出了它们作为一种潜在诊断剂的价值。

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