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

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.

Nanotechnology for cardiovascular diseases

“…Besides, the combination of MRI and optical imaging for dual-modal imaging could effectively relieve their respective drawbacks: the low sensitivity of MRI and the poor tissue penetration and spatial resolution of optical imaging ( Document S2 ). 108 , 132 , 133 , 134 , 135 , 136 , 137 , 138

Figure 3 Multimode imaging strategies for specific and accurate detection of atherosclerotic plaques and thrombi (A) Marcoflor nanotracer for PET/MRI to visualize atherosclerosis. 127 In PET/MRI experiment, 18F-Macroflor PET imaging detected changes in macrophage population size, while molecular MRI reported on increasing or resolving inflammation (copyright Springer Nature, 2017).

…”

Iron Oxide Nanoparticles in Regenerative Medicine and Tissue Engineering

“…For early detection of atherosclerotic plaques and activated platelets, which play a central role in thrombosis, atherosclerosis and inflammation, Prévot et al coupled the platelet-specific scFv-Fc TEG4-2C antibody with a IONP-containing magnetic oil-in-water nano-emulsion and achieved significant labeling of atheroma plaques both in vitro and ex vivo in animal models using magnetic particle imaging (MPI) and MRI [173]. Specific targeting of platelets was also achieved by using a single chain antibody (scFv) [174,175]. Coupling of scFv to IONPs or cells provided the possibility of molecular imaging and cell homing in cardiovascular and inflammatory diseases.…”

Nanotechnology for Molecular Imaging of Atherosclerosis: Current Design and Approaches

“…The success of functionalized MRI-NIRF imaging was obtained by the conjugation of profilin-1 antibodies with β-cyclodextrin magnetic nanoparticles (PFN1-CD-MNPs) loaded NIRF cyanine dye, that showed significantly high fluorescence signals in the aorta, leading to better atherosclerotic plaque targeted-imaging [73]. Another research on MRI-NIRF imaging of versatile ultra-small super-paramagnetic iron oxide (VUSPIO) similarly demonstrated excellent fluorescence signal in the plaque site, indicating potential of functional VUSPIO as a biocompatible and atheroma-specific diagnostic agent [85].…”