Abstract
We investigate the distribution and biological effects of polyethylene glycol (PEG)-coated magnetite (Fe3O4@PEG) nanoparticles (~30 nm core size, ~51 nm hydrodynamic size, 2 mg Fe/kg/day, intravenously, for two days) in the aorta and liver of Wistar–Kyoto (WKY) and spontaneously hypertensive rats (SHR). Fe3O4@PEG had no effect on open-field behaviour but reduced the blood pressure (BP) of Fe3O4@PEG-treated SHR (SHRu) significantly, compared to both Fe3O4@PEG-treated WKY (WKYu) and saline-treated control SHR (SHRc). The Fe3O4@PEG content was significantly elevated in the aorta and liver of SHRu vs. WKYu. Nitric oxide synthase (NOS) activity was unaltered in the aorta, but significantly increased in the liver of SHRu vs. SHRc. In the aorta, Fe3O4@PEG treatment increased eNOS, iNOS, NRF2, and DMT1 gene expression (considered main effects). In the liver, Fe3O4@PEG significantly elevated eNOS and iNOS gene expression in SHRu vs. SHRc, as well as DMT1 and FTH1 gene expression (considered main effects). Noradrenaline-induced contractions of the femoral arteries were elevated, while endothelium-dependent contractions were reduced in SHRu vs. SHRc. No differences were found in these parameters in WKY rats. In conclusion, the results indicated that the altered haemodynamics in SHR affect the tissue distribution and selected biological effects of Fe3O4@PEG in the vasculature and liver, suggesting that caution should be taken when using iron oxide nanoparticles in hypertensive subjects.
Highlights
Metal nanoparticles (NPs), including ultra-small superparamagnetic iron oxide nanoparticles (USPIONs), possess strong potential for various biomedical applications [1,2,3]
We investigated whether high blood pressure (BP) affects the presence of USPIONs in the bloodstream and their incorporation into selected tissues, which could be associated with increased USPION-derived iron content in the aorta and liver, and manifested by altered spontaneous behaviour, BP changes, altered vascular function, and genomic changes
USPIONs to enter the vascular smooth muscle cells. In agreement with these findings, we found elevated gene expression of divalent metal transporter 1 (DMT1), as well as nuclear factors nuclear factor erythroid 2-related factor 2 (NRF2) and peroxisome proliferatoractivated receptor gamma (PPARγ)—which are involved in the regulation of various genes, including those involved in antioxidant defence and iron metabolism [14,38,39]—when calculated as the main effect of treatment, in both rat strains
Summary
Metal nanoparticles (NPs), including ultra-small superparamagnetic iron oxide nanoparticles (USPIONs), possess strong potential for various biomedical applications [1,2,3]. It is well-known that the properties and biological effects of USPIONs are considerably dependent on their size, physicochemical factors, and surface modification. PEGylation has been shown to reduce the toxic effects of uncoated iron oxide NPs [6,7], including oxidative damage to DNA, proteins, and membrane lipids, as well as interference with the innate iron metabolism in mammals [2]. The potential negative effects of iron oxide nanoparticles (IONs) in vivo result from various factors [8]—mainly from their degradation followed by free iron release after decomposition of their coating. Elevated free iron levels may lead to oxidative stress, as well as affecting biogenic iron homeostasis, through altered production of hepatic hormone hepcidin (encoded by HAMP gene), a main regulator of iron absorption in the enterocyte [9,10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
