(136a) Toxicity of Orally Administered Magnetic Imaging Nanoprobes in an Inflammatory Intestinal Epithelial Cell Model | AIChE

(136a) Toxicity of Orally Administered Magnetic Imaging Nanoprobes in an Inflammatory Intestinal Epithelial Cell Model


Asad, S. - Presenter, Uppsala University
Teleki, A., Uppsala University
Bergström, C. A. S., Uppsala University
Introduction: 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.

Methods: Pure iron oxide and SiO2-coated iron oxide nanoparticles are 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.

Results: Global proteomics of inflamed Caco-2 cell model has shown the upregulation of biomarkers, such as ICAM1, in the apical side of the plasma membrane.3 Caco-2 cell viability was not altered by the exposure to SiO2-coated SPIONs, which indicates an increased biocompatibility due to the coating layer. As expected, the inflamed cell model demonstrated a higher leakiness across the monolayer compared to the healthy cells. However, the monolayer integrity of the inflamed cell model was not found to be significantly worsened after 24 h of exposure to the SiO2-coated SPIONs. These results suggests that SPIONs used as MRI imaging probes would not impair the inflamed state during an active inflammation.

Conclusions: 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).