Biocompatibility of cerium dioxide and silicon dioxide nanoparticles with endothelial cells

Abstract

SummaryCerium dioxide (CeO2) and silicon dioxide (SiO2) nanoparticles are of widespread use in modern life. This means that human beings are markedly exposed to them in their everyday life. Once passing biological barriers, these nanoparticles are expected to interact with endothelial cells, leading to systemic alterations with distinct influences on human health. In the present study we observed the metabolic impact of differently sized CeO2 (8 nm; 35 nm) and SiO2 nanoparticles (117 nm; 315 nm) on immortalized human microvascular (HMEC-1) and primary macrovascular endothelial cells (HUVEC), with particular focus on the CeO2 nanoparticles. The characterization of the CeO2 nanoparticles in cell culture media with varying serum content indicated a steric stabilization of nanoparticles due to interaction with proteins. After cellular uptake, the CeO2 nanoparticles were localized around the nucleus in a ring-shaped manner. The nanoparticles revealed concentration and time, but no size-dependent effects on the cellular adenosine triphosphate levels. HUVEC reacted more sensitively to CeO2 nanoparticle exposure than HMEC-1. This effect was also observed in relation to cytokine release after nanoparticle treatment. The CeO2 nanoparticles exhibited a specific impact on the release of diverse proteins. Namely, a slight trend towards pro-inflammatory effects, a slight pro-thrombotic impact, and an increase of reactive oxygen species after nanoparticle exposure were observed with increasing incubation time. For SiO2 nanoparticles, concentration- and time-dependent effects on the metabolic activity as well as pro-inflammatory reactions were detectable. In general, the effects of the investigated nanoparticles on endothelial cells were rather insignificant, since the alterations on the metabolic cell activity became visible at a nanoparticle concentration that is by far higher than those expected to occur in the in vivo situation (CeO2 nanoparticles: 100 µg/mL; SiO2 nanoparticles: 10 µg/mL).

On the Operational Aspects of Measuring Nanoparticle Sizes

“…While 70 nm-sized SiO 2 particles were found to enter into the cell nucleus, it was also observed for NPs of larger size (>200 nm) [21]. Distinct effects of TiO 2 and SiO 2 have been observed on endothelial cells depending on cell types, concentrations, and exposure time [26] and similarly for CeO 2 (8 and 35 nm) and SiO 2 (177 and 315 nm) NPs [27]. The size of NPs has been shown to be an important parameter for the destabilization of biological membranes but it was found that only large NPs (>100 nm) induced an increased disruption of membrane domain structures [28].…”

Fate of cerium dioxide nanoparticles in endothelial cells: exocytosis

“…The impact of nanotechnology in various branches of industry and in medicine has increased in the last years, which is reflected by nanoparticles’ use, for example, in certain products of the food sector (Chaudhry et al 2008 ), or for prospective medical applications [e.g., for optical imaging (Jiang et al 2010 ), for cancer therapy (Hilger 2013 ; Johannsen et al 2005 ), or for drug delivery (Cho et al 2008 )], as contrast agents (Hahn et al 2011 ), in cosmetics like sun protection agents (Strobel et al 2014a ) etc. Therefore, humans are increasingly faced with nanoparticles in daily life.…”

Toxicity and Protective Effects of Cerium Oxide Nanoparticles (Nanoceria) Depending on Their Preparation Method, Particle Size, Cell Type, and Exposure Route

“…However, as noted in most of these reviews, toxicity tests are often hardly reproducible among different research groups. For example, the size of NPs, [4] their surface properties, [5] the type of cells, [4] and the exposure method [6] all influence the outcome of studies on their toxicity in such a way that it may lead to different results. On the other hand, the increased use of NPs and nanoparticulate materials as well as their potential in various applications render the study of their toxicity highly essential.…”