Metal-organic Framework [H2NMe2]3 [Tb(PDA)3] Induces Cytotoxic Effects and Changes DNA Methylation-related Gene Expression in a Human Fibroblast Cell Line

Abstract In this work, we describe the effect of six concentrations (0.05, 0.1, 0.2, 0.4, 0.8 and 1.6 mg/mL) of a metal-organic framework [H2NMe2]3 [Tb(PDA)3] on the viability of human fibroblast cells (hFB) after 48 h of exposure. The terbium metal-organic framework may be utilized for a variety of environmental and human health applications due to its luminescent properties and high thermal and water stability. However, the cytotoxic and epigenetic effects of lanthanide MOFs have not been fully elucidated to date. Therefore, we evaluated the cytotoxic effects, internalization and changes in DNA methylation-associated gene expression induced by exposing hFB to Tb-MOF. The images obtained by SEM, confocal microscopy and EDS analysis demonstrated the internalization of Tb-MOF at concentrations as low as 0.05 mg/mL, as well as dose-dependent toxicity in the fibroblasts, with a mean inhibitory concentration (IC50) of 0.260 ± 0.012 mg/mL being observed. Additionally, we detected significant changes in the gene expression levels of DNA methyltransferases and demethylases (important regulators of development of cell) due to the presence of Tb-MOF, suggesting that Tb-MOF could contribute to cell death and destabilize the genome even at low concentrations. These results of this study may establish a foundation for future research attempting to develop and apply secure nanomaterials (e.g., MOFs) to minimize damage to the environment and human health.