Long-term administration of low-dose selenium nanoparticles with different sizes aggravated atherosclerotic lesions and exhibited toxicity in apolipoprotein E-deficient mice.

Exploration of long-term in vivo effects of nanomaterials, particularly those with potential biomedical applications, is quite important for better understanding and evaluating their biosafety. Selenium nanoparticles (SeNPs) has been considered as a good candidate in biomedical applications due to its high bioavailability, considerable biological activity, and low toxicity. However, its long-term biological effects and biosafety remain unknown. Our previous study demonstrated that 8-week supplementation with SeNPs (50 μg Se/kg/day) was safe and had an anti-atherosclerotic activity in apolipoprotein E-deficient (ApoE-/-) mice, a well-known animal model of atherosclerosis. As a chronic disease, atherosclerosis needs long-term drug therapy. The aim of this study is to investigate the long-term effects of SeNPs with different sizes on atherosclerotic lesions and their biosafety in ApoE-/- mice fed with a high fat diet. Unexpectedly, the results showed that 24-week administration of SeNPs even at a low dose (50 μg Se/kg/day) aggravated atherosclerotic lesions. Furthermore, SeNPs exacerbated oxidative stress by inhibiting the activities of antioxidant enzymes and the expression of antioxidant selenoenzymes. SeNPs also exacerbated hyperlipidaemia by inducing hepatic lipid metabolic disorder. In the meanwhile, SeNPs aggravated organ injury, especially liver and kidney injury. The above adverse effects of SeNPs were size dependent: SeNPs with the size of 40.4 nm showed the highest adverse effects among the SeNPs with three sizes (23.1 nm, 40.4 nm, and 86.8 nm). In conclusion, the present work shows that long-term administration of low-dose SeNPs aggravated atherosclerotic lesions by enhancing oxidative stress and hyperlipidaemia in ApoE-/- mice, indicative of cardiovascular toxicity. Moreover, long-term administration of SeNPs led to injury to liver and kidney. These results offer novel insights for better understanding the biosafety of SeNPs and other biomedical nanomaterials.