Anthropogenic Iron Oxide Nanoparticles Induce Damage to Brain Microvascular Endothelial Cells Forming the Blood-Brain Barrier

Article type: Research Article

Authors: Gárate-Vélez, Lorena^a | Escudero-Lourdes, Claudia^b | Salado-Leza, Daniela^c | González-Sánchez, Armando^a | Alvarado-Morales, Ildemar^b | Bahena, Daniel^d | Labrada-Delgado, Gladis Judith^{a; e} | Rodríguez-López, José Luis^{a; *}

Affiliations: [a] Advanced Materials Department, IPICYT, A.C., San Luis Potosí, S.L.P., México | [b] Laboratorio de Inmunotoxicología, Facultad de Ciencias Químicas, Centro de Investigación y Estudios de Posgrado (CIEP), Universidad Autónoma de San Luis Potosí, San Luis Potosí, S.L.P., México | [c] Cátedras CONACYT, Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, San Luis Potosí, S.L.P., México | [d] Laboratorio Avanzado de Nanoscopía Electrónica, Centro de Investigación y de Estudios Avanzados, Instituto Politécnico Nacional, Gustavo A. Madero, México | [e] National Laboratory Research for Nanoscience and Nanotechnology (LINAN), IPICYT, A.C., San Luis Potosí, S.L.P., México

Correspondence: [*] Correspondence to: José Luis Rodríguez-López, Advanced Materials Department, IPICYT, A.C., Camino Presa San José 2055, Lomas 4a Secc., 78216 San Luis Potosí, S.L.P., México. E-mail: [email protected].

Abstract: Background:Iron nanoparticles, mainly in magnetite phase (Fe3O4 NPs), are released to the environment in areas with high traffic density and braking frequency. Fe3O4 NPs were found in postmortem human brains and are assumed to get directly into the brain through the olfactory nerve. However, these pollution-derived NPs may also translocate from the lungs to the bloodstream and then, through the blood-brain barrier (BBB), into the brain inducing oxidative and inflammatory responses that contribute to neurodegeneration. Objective:To describe the interaction and toxicity of pollution-derived Fe3O4 NPs on primary rat brain microvascular endothelial cells (rBMECs), main constituents of in vitro BBB models. Methods:Synthetic bare Fe3O4 NPs that mimic the environmental ones (miFe3O4) were synthesized by co-precipitation and characterized using complementary techniques. The rBMECs were cultured in Transwell® plates. The NPs-cell interaction was evaluated through transmission electron microscopy and standard colorimetric in vitro assays. Results:The miFe3O4 NPs, with a mean diameter of 8.45±0.14 nm, presented both magnetite and maghemite phases, and showed super-paramagnetic properties. Results suggest that miFe3O4 NPs are internalized by rBMECs through endocytosis and that they are able to cross the cells monolayer. The lowest miFe3O4 NPs concentration tested induced mid cytotoxicity in terms of 1) membrane integrity (LDH release) and 2) metabolic activity (MTS transformation). Conclusion:Pollution-derived Fe3O4 NPs may interact and cross the microvascular endothelial cells forming the BBB and cause biological damage.

Keywords: Blood-brain barrier, cytotoxicity, in vitro , magnetite nanoparticles

DOI: 10.3233/JAD-190929

Journal: Journal of Alzheimer's Disease, vol. 76, no. 4, pp. 1527-1539, 2020