173 Infused silica nanoparticles compromise vascular function in small mesenteric arteries

Abstract

<h3>Introduction</h3> The emergence of nanomedicine, involving the intravenous injection of tracking agents (such as dye-encapsulated silica nanoparticles [SiNPs]) for imaging diagnostic and therapeutic purposes may hold a biosafety concern specifically to the vascular system. Our previous findings suggest that SiNPs of 100 and 200 nm size have no detrimental effect on conduit arterial function. However, their effect on small size vessels, which play an important role in controlling blood perfusion into tissues, has not been investigated. <h3>Methods and results</h3> Vasoconstrictor and vasodilator responses of mesenteric arteries (MAs) from male Wistar rats were assessed using pressure myography before and 30 min after intravascular infusion of SiNPs. Our data show that SiNPs (100 nm size at 5.32 × 10¹¹ NPs/mL dose) compromised the contractile responses to phenylephrine (Phe) (n = 5; p &lt; 0.01). SiNPs also attenuated the endothelium-dependent (acetylcholine) dilator responses in high potassium (KPSS) and Phe-pre-contracted vessels following their rapid uptake into the cytoplasm of endothelial cells <i>ex vivo</i> as well as <i>in vivo</i> (At 100 nM Ach, the mean percentage dilation was 78.77 ± 8.58% vs. 36.30 ± 5.07% after incubation in PSS and SiNPs respectively, p &lt; 0.001). The acute exposure to SiNPs did not alter the endothelium-independent relaxation to sodium nitroprusside (n = 4). SiNPs were biodistributed in trace amounts into different tissues; including MAs, aortic vessel, liver and spleen <i>in vivo</i>. The physiological changes were accompanied by a decrease in the phosphorylated levels of both extracellular-signal-regulated kinase (ERK) and protein kinase Akt demonstrated by proteomic analysis. <h3>Conclusions</h3> Findings suggest that SiNPs may affect microvessel function <i>via </i>modulation of the ERK/AKT pathway. Our data highlight the need to identify strategies that can help minimise possible detrimental effects of nanoparticles on arterial function.