Differences in Distribution and Biological Effects of F 3 O 4 @PEG Nanoparticles in Normotensive and Hypertensive Rats-Focus on Vascular Function and Liver.

We investigate the distribution and biological effects of polyethylene glycol (PEG)-coated magnetite (Fe 3 O 4 @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). Fe 3 O 4 @PEG had no effect on open-field behaviour but reduced the blood pressure (BP) of Fe 3 O 4 @PEG-treated SHR (SHRu) significantly, compared to both Fe 3 O 4 @PEG-treated WKY (WKYu) and saline-treated control SHR (SHRc). The Fe 3 O 4 @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, Fe 3 O 4 @PEG treatment increased eNOS, iNOS, NRF2 , and DMT1 gene expression (considered main effects). In the liver, Fe 3 O 4 @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 Fe 3 O 4 @PEG in the vasculature and liver, suggesting that caution should be taken when using iron oxide nanoparticles in hypertensive subjects.