Effects of different doses of 2,3‐dimercaptosuccinic acid‐modified Fe₂O₃nanoparticles on intercalated discs in engineered cardiac tissues

Abstract Although iron oxide nanoparticles (IRONs) were applied in clinical magnetic resonance imagingin vivoand magnetic tissue engineeringin vitrowidely, the underlying effects of IRONs on the development of cardiomyocytes especially the intercellular junctions, intercalated discs (IDs), remain an unknown issue. Given the critical role of three‐dimensional (3D) engineered cardiac tissues (ECTs) in evaluation of nanoparticles toxicology, it remained necessary to understand the effects of IRONs on IDs assembly of cardiomyocytes in 3D environment. In this study, we first reconstituted collagen/Matrigel based ECTsin vitroand prepared IRONs with 2,3‐dimercaptosuccinic acid (DMSA‐IRONs). We found that the internalization of DMSA‐IRONs by cardiac cells in dose‐dependent manner was not associated with the cell distribution in 3D environment by determination of Prussian blue staining and transmission electronic microscopy. Significantly, through determination of western blotting and immunofluorescence of connexin 43, N‐cadherin, desmoplakin, and plakoglobin, DMSA‐IRONs enhanced the assembly of gap junctions, decreased mechanical junctions (adherens junctions and desmosomes) of cardiac cells but not in dose‐dependent manner in ECTs at seventh day. In addition, DMSA‐IRONs increased the vesicles secretion of cardiac cells in ECTs apparently compared to control groups. Overall, we conclude that the internalization of DMSA‐IRONs by cardiac cells in dose‐dependent manner enhanced the assembly of electrochemical junctions and decreased the mechanical related microstructures. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 121–130, 2018.