(171c) Toxicity of Orally Administered Magnetic Imaging Nanoprobes in an Inflammatory Intestinal Epithelial Cell Model

SiO₂-coated superparamagnetic iron oxide nanoparticles (SPION) can be efficiently produced in a scalable, single-step flame process.^1,2 The SiO₂-layer on the particle surface facilitates subsequent chemical modifications, and the magnetic iron oxide core makes the SPIONs suitable as MRI contrast agents. We hypothesized that functionalizing SPIONs with ligands that target overexpressed biomarkers in the gastrointestinal tract (GIT) can allow non-invasive imaging of diseases such as inflammatory bowel disease (IBD) in vivo. Biomarkers in preclinical IBD models include ICAM1,³ which could be targeted using functionalized SPIONs. However, exposing damaged and inflamed cells to such functionalized nanoparticles might have the potential to cause immunotoxicity and compromise their safe use as contrast agents. Pure iron oxide and SiO₂-coated iron oxide nanoparticles were made through flame spray pyrolysis.¹ Monoclonal antibody anti-ICAM1 is conjugated onto the SiO₂-coated particle surface using click chemistry to target the IBD associated biomarker ICAM1. Filter-grown Caco-2 cells are treated with a mixture of inflammatory inducing agents to resemble the inflamed state of IBD. Both the antibody-functionalized, non-functionalized and pure SPION particles are evaluated for their cytotoxic and genotoxic effects, as well as the morphological changes in the cell monolayer. Cytotoxicity and genotoxicity is examined using CellTiterGlo assay and Comet assay, respectively. Cell integrity is examined by measuring permeability of Lucifer yellow across the cell monolayer. A dose dependent correlation between SPIONs and toxicity is expected to be found. Global proteomics of inflamed Caco-2 cell model has shown the upregulation of biomarkers, such as ICAM1, in the apical plasma membrane.³ These results provide guidance for appropriate functionalization of SPIONs to target the inflamed tissue. The inflamed cell model is likely to demonstrate a higher sensitivity to the SPIONs compared to the healthy cell monolayer. Adverse toxic effects of nanomaterial based imaging probes for use in vivo is important to assess. Evaluation of cytotoxic and genotoxic effects, as well as changes in permeability of inflamed Caco-2 cell monolayers provide an estimation of the safety to use functionalized SPION as a diagnostic tool in vivo.

References: [1] Teleki, A., M. Suter, P.R. Kidambi, O. Ergeneman, F. Krumeich, B.J. Nelson, and S.E. Pratsinis, Chem. Mater. 21, 10, (2009). [2] Teleki, A., F.L. Haufe, A.M. Hirt, S.E. Pratsinis, and G.A. Sotiriou, RSC Adv. 6, 26, (2016). [3] Asad, S., Wegler, C., D. Ahl, C.A.S. Bergström, M. Phillipson, P. Artursson and A. Teleki, J. Pharm. Sci. 110, 1 (2021).