The effect of intravenous administration to rats of magnetite nanoparticles with various shells on the functional state and morphology of the endothelium and on antioxidant status

Background. Today, the development of nanoparticles for targeted drug delivery is underway. A separate place is occupied by magnetic nanoparticles based on iron oxides (MNPs) due to their chemical stability, relatively high biocompatibility, and comparative ease of preparation. Unmodified MNPs can easily be oxidized, that can to lead to toxic effects and a loss of magnetic and colloidal stability, in order to avoid these effects, it is necessary to coat their surface, then to study of their effect on vascular endothelium and antioxidant status. Objective. The aim of the work was to study the effect of intravenous injection to rats of magnetic nanoparticles of iron oxide with various shells on the functional condition and morphology of the endothelium and on antioxidant status. Design and methods. In this work, we used colloidal solutions of magnetite nanoparticles (MNP) in a 0.9 % NaCl solution. MNPs were coated with albumin (MNP + albumin), polylactide (MNP + polylactide) and polysaccharide (MNP + polysaccharide). The study was performed on male rats of the Wistar SPF-category. MNP were injected once into the lateral tail vein of rats. Vascular morphology was studied by histological methods. The functional activity of the endothelium was studied by wire myography method. The concentration of nitric oxide and the concentration of lipid peroxidation products were evaluated by enzyme immunoassay. Total antioxidant activity and total antioxidant capacity of plasma were evaluated by using the method of luminol-activated chemiluminescence. Results. A single intravenous injection to rats of MNP + albumin and MNP + polylactide does not provide changes in vascular reactivity, however, the introduction of MNP + polysaccharide causes a decrease in endothelium-dependent relaxation while maintaining the ability to reduce. The studied types of magnetic nanoparticles do not affect the metabolic activity of the endothelium and vascular morphology. It was found that the introduction of the studied agents causes a decrease in the level of lipid peroxidation. MNP + albumin, MNP + polylactide, and MNP + polysaccharide, when it injected once intravenously, provide a similar effect, but different mechanisms of realization on the antioxidant status. Conclusion. The obtained data indicate that the studied species of MNPs have equal biocompatibility when they are once administered intravenously to rats.

antioxidant status, biocompatibility, chemiluminescence, endothelium, magnetic nanoparticles, wire myography

1. Reddy L, Arias J, Nicolas J, et al. Magnetic nanoparticles: design and characterization, toxicity and biocompatibility, pharmaceutical and biomedical applications. Chemical Reviews. 2012; 112(11):58185878.

2. Dobson J. Magnetic nanoparticles for drug delivery. Drug Development Research. 2006; 67:55–60.

3. Sun C, Lee J, Zhang M. Magnetic nanoparticles in MR imaging and drug delivery. Advanced drug delivery reviews. 2008; 60(11):1252–1265.

4. Liu X, Choo E, Ahmed A, et al. Magnetic nanoparticle-loaded polymer nanospheres as magnetic hyperthermia agents. Journal of Materials Chemistry B. 2014; 2(1):120–128.

5. Haun JB, Yoon T-J, Lee H, Weissleder R. Magnetic nanoparticle biosensors. WIREs: Nanomedicine and Nanobiotechnology. 2010; 2(3):291–304.

6. Gupta AK, Curtis AS. Lactoferrin and ceruloplasmin derivatized superparamagnetic iron oxide nanoparticles for targeting cell surface receptors. Biomaterials. 2004; 25(15): 3029–3040.

7. Sun S, Zeng H, Robinson DB, et al. Monodisperse MFe2O4 (M=Fe, Co, Mn) nanoparticles. Journal of the American Chemical Society. 2004; 126(1):273–279.

8. Mandal S, Chaudhuri K. A simple method for the synthesis of ultrafine carbon nanoparticles and its interaction with bovine serum albumin. Advanced Science Letters. 2012; 5(1):139–143.

9. Van Sliedregt A, Radder AM, de Groot K, van Blitterswijk CA. In vitro biocompatibility testing of polylactides Part I Proliferation of different cell types. Journal of Materials Science: Materials in Medicine. 1992;3:365–370.

10. Toropova YaG, Zelinskaya IA, Markitanova AC, et al. The influence of magnethite nanoparticles and FemOn- SiO2 colloidal particles on endothelium functional statement after intravenous injection in rats. Russian Journal of physiology = Rossiyskiy fiziologicheskiy zhurnal im. I.M. Sechenoval. 2017; 103 (12):1416–1424. In Russian.

11. Mandal S, Chaudhuri K. Magnetic core-shell nanoparticles for biomedical applications. In: Sharma S, (eds) Complex Magnetic Nanostructures. Cham: Springer International Publishing AG, 2017:425–453.

12. Toropova YaG, Golovkin AS, Malashicheva AВ, et al. In vitro toxicity of FemOn, FemOn-SiO2 composite, and SiO2-FemOn core-shell magnetic nanoparticles. International Journal of Nanomedicine. 2017; 12: 593–603.

13. Waynforth HB, Flecknell PA. Experimental and Surgical Technique in the Rat. 2nd ed. London: Academic Press, 1992: p. 382.

14. Toropova YaG, Pechnikova NA, Zelinskaya IA, et al. Hemocompatibility of magnetic magnethite nanoparticles and magnetite-silica composites in vitro. Bulletin of Siberian Medicine = Byulleten’ sibirskoy meditsiny. 2018; 17(3):157–167. In Russian.

15. Zelinskaya IA, Toropova YaG. Wire myography in modern scientific researches: methodical aspects. Regional blood circulation and microcirculation = Regionarnoe krovoobrashchenie i mikrotsirkulyatsiya. 2018;17(1):83–89. In Russian.

16. Vladimirov YuA, Proskurnina EV. Free radicals and cell chemiluminescence. Advances in biological chemistry = Uspekhi biologicheskoy khimii. 2009; 49: 341–388. In Russian.

17. Uotila J, Kirkkola AL, Rorarius M, et al. The total peroxyl radical-trapping ability of plasma and cerebrospinal fluid in normal and preeclamptic parturients. Free Radical Biology and Medicine. 1994;16(5):581–590.

18. Petrenko VM. The reticular structure of the microcirculatory. University proceedings. Volga region. Medical sciences = Izvestiya vysshikh uchebnykh zavedeniy. Povolzhskiy region. Meditsinskie nauki. 2010; 13(1): 37–46. In Russian.

19. Tybinka AM, Paladiychuk ER. Characteristic of the blood vessels of the intestine and its mesentery. Scientific messenger of LNU of veterinary medicine and biotechnologies = Naukovyj visnyk LNUVMBT imeni S.Z. G’zhyc’kogo. 2015; 17 (2): 232–240. In Russian.

20. Junqueira L, Carneiro J. Junqueira’s basic histology. Text and atlas. 11th ed. New York: McGraw-Hill, 2005. p. 544.

21. Korzhevskiy DE, Kolos EA, Karpenko MN, et al. Histochemical determination of metals. SPb: SpetsLit, 2016. p. 63. In Russian.