Optical and X-ray attenuation properties of hafnium oxide nanoparticles surface functionalized with fucoidan: toward the early diagnosis of atherothrombotic diseases

Atherothrombosis is the main cause of death worldwide. An early diagnosis of this pathology is necessary to avoid serious clinical events. In this study, we report hafnium oxide nanoparticles (HfO2 NPs) designed as a CT contrast agent for an emerging imaging technology named spectral photon counting computed tomography (SPCCT). SPCCT allows the specific detection and quantification of the contrast agent concentration, according to its K-edge. HfO2 NPs were surface functionalized with fucoidan, a sulfated polysaccharide that has high affinity for P-selectin considered as a glycoprotein biomarker in atherothrombosis, and citrate ions as a control ligand. The physicochemical characterization of fucoidan coated HfO2 NPs (HfO2@fucoidan NPs) was finely studied, and the influence of the coating agent on the UV absorption and photoluminescence properties was evidenced. The in vitro flow adhesion assay showed the specific binding of HfO2@fucoidan NPs to activated platelets under arterial flow. These NPs showed excellent biocompatibility on the HUVEC cell line and the enhancement of cell viability. Phantoms performed with SPCCT show that the value of the attenuation rate (A. R.) of HfO2@fucoidan NPs (27 HU ml mg(-1)) is greater (x1.7) than that of HfO2@citrate NPs (17 HU ml mg(-1)). A good correlation between the measured concentration and the references was obtained. These synthesized HfO2@fucoidan NPs appear as a new candidate for X-ray imaging for the molecular-scale diagnosis of atherothrombosis.

Automated summary

In this study, hafnium oxide nanoparticles were designed as a CT contrast agent for spectral photon counting computed tomography. The nanoparticles were surface functionalized with fucoidan, a sulfated polysaccharide that has high affinity for P-selectin, and citrate ions as a control ligand. The in vitro flow adhesion assay showed specific binding of the nanoparticles to activated platelets under arterial flow. SPECTCT experiments demonstrated that the nanoparticles had a higher absorption rate and a good correlation between the measured concentration and the references. Therefore, these functionalized hafnium oxide nanoparticles have the potential to be used for X-ray imaging and molecular-scale diagnosis of atherothrombosis.