Gold Nanoparticles Supported on Ceria Nanoparticles Modulate Leukocyte–Endothelium Cell Interactions and Inflammation in Type 2 Diabetes

Abstract

Diabetes; Gold-ceria nanoparticle; Inflammation

Diabetes; Nanopartícula de oro-ceria; Inflamación

Diabetis; Nanopartícula d'or-cèria; Inflamació

Gold-ceria nanoparticles (Au/CeO2) are known to have antioxidant properties. However, whether these nanoparticles can provide benefits in type 2 diabetes mellitus (T2D) remains unknown. This work aimed to study the effects of Au/CeO2 nanoparticles at different rates of gold purity (10, 4.4, 1.79 and 0.82) on leukocyte–endothelium interactions and inflammation in T2D patients. Anthropometric and metabolic parameters, leukocyte–endothelium interactions, ROS production and NF-κB expression were assessed in 57 T2D patients and 51 healthy subjects. T2D patients displayed higher Body Mass Index (BMI) and characteristic alterations in carbohydrate and lipid metabolism. ROS production was increased in leukocytes of T2D patients and decreased by Au/CeO2 at 0.82% gold. Interestingly, Au/CeO2 0.82% modulated leukocyte–endothelium interactions (the first step in the atherosclerotic process) by increasing leukocyte rolling velocity and decreasing rolling flux and adhesion in T2D. A static adhesion assay also revealed diminished leukocyte–endothelium interactions by Au/CeO2 0.82% treatment. NF-κB (p65) levels increased in T2D patients and were reduced by Au/CeO2 treatment. Cell proliferation, viability, and apoptosis assays demonstrated no toxicity produced by Au/CeO2 nanoparticles. These results demonstrate that Au/CeO2 nanoparticles at 0.82% exert antioxidant and anti-inflammatory actions in the leukocyte–endothelium interaction of T2D patients, suggesting a protective role against the appearance of atherosclerosis and cardiovascular diseases when this condition exists.

This study was financed by grants PI22/00424, PI19/00838, PI19/0437 and CIBERehd CB06/04/0071 by Carlos III Health Institute and by the European Regional Development Fund (ERDF “A way to build Europe”); ACIF/2020/370 (P.D.-P.), GRISOLIAP/2019/091 (F.C.) and APOSTD/2020/145 (S.L.-D); S.R.-L is recipient of a Maria Zambrano fellowship ZA21-049, from the requalification of the Spanish university system from the Ministry of Universities of the Government of Spain, financed by the European Union, Next Generation EU, PROMETEO/2019/027 by the Ministry of Health of the Valencian Regional Government. C.L.-M. was supported by Erasmus+ internship grant through Uppsala University, Sweden.