Response of the Endogenous Antioxidant Defense System Induced in RAW 264.7 Macrophages upon Exposure to Dextran-Coated Iron Oxide Nanoparticles

Mihaela Balas; Simona Liliana Iconaru; Anca Dinischiotu; Nicolas Buton; Daniela Predoi

doi:10.3390/pharmaceutics15020552

Response of the Endogenous Antioxidant Defense System Induced in RAW 264.7 Macrophages upon Exposure to Dextran-Coated Iron Oxide Nanoparticles

Pharmaceutics. 2023 Feb 7;15(2):552. doi: 10.3390/pharmaceutics15020552.

Authors

Mihaela Balas¹, Simona Liliana Iconaru², Anca Dinischiotu¹, Nicolas Buton³, Daniela Predoi²

Affiliations

¹ Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 91-95 Splaiul Independentei, 050095 Bucharest, Romania.
² HORIBA Jobin Yvon S.A.S., 6-18, Rue du Canal, CEDEX, 91165 Longjumeau, France.
³ National Institute of Materials Physics, 405A Atomistilor Street, 077125 Magurele, Romania.

Abstract

Presently, iron oxide nanoparticles are the only ones approved for clinical use as contrast agents in magnetic resonance imaging (MRI). Even though there is a high demand for these types of nanoparticles both for clinical use as well as for research, there are difficulties in obtaining stable nanoparticles with reproducible properties. In this context, in this study, we report the obtaining by an adapted coprecipitation method of dextran-coated maghemite nanoparticles (ɤ-Fe₂O₃ NPs). The morphology and structure of the dextran-coated maghemite nanoparticles (ɤ-Fe₂O₃ NPs) were determined using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The TEM and SEM micrographs highlighted the obtaining of particles of nanometric size and spherical shape morphology. Furthermore, the high-resolution transmission electron microscopy (HRTEM), as well as selected area diffraction (SAED), revealed that the obtained samples presented the structure of cubic maghemite. In this study, we also explored the effects of the co-precipitation synthesized dextran-coated maghemite nanoparticles (ɤ-Fe₂O₃ NPs) on the redox status of macrophages. For cytotoxicity evaluation of these NPs, murine macrophages (RAW 264.7 cell line) were exposed to different concentrations of dextran-coated maghemite nanoparticles (ɤ-Fe₂O₃ NPs) corresponding to 0-500 μg Fe³⁺/mL and incubated for 24, 48, and 72 h. Intracellular iron uptake, changes in the oxidative stress parameters (reactive oxygen species production and malondialdehyde level), and the activity of antioxidant enzymes, as well as GSH concentration in cells, were evaluated after incubation with a lower (50 μg Fe³⁺/mL) and higher (500 μg Fe³⁺/mL) dose of NPs. The results indicated a significant decrease in RAW 264.7 cell viability after 72 h in the presence of NPs at concentrations above 25 μg Fe³⁺/mL. An important accumulation of NPs, dependent on dose and exposure time, was detected in macrophages, but it induced only a limited raise in the oxidative status. We showed here that the antioxidant capacity of RAW 264.7 macrophages was efficient in counteracting dextran-coated maghemite nanoparticles (ɤ-Fe₂O₃ NPs) toxicity even at higher doses.

Keywords: RAW 264.7 macrophages; antioxidant enzyme activity; dextran; iron oxide nanoparticles; oxidative stress.

Grants and funding

This research received no external funding.