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 imaging in vivo and magnetic tissue engineering in vitro widely, 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 threedimensional (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 ECTs in vitro and 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 dosedependent 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.

Cerium- and Iron-Oxide-Based Nanozymes in Tissue Engineering and Regenerative Medicine

“…Western blotting showed increased expression of Cx43 in a dose-dependent manner, thus demonstrating the ability of IO-NPs in promoting gap junction assembly ( Figure 2B,E). As such, these results show how different functions were exerted by the IO-NPs when comparing a two-dimensional (2D) environment [65] with a three-dimensional (3D) environment [66].…”

“…While the internalized IO-NPs showed in vitro peroxidase-like activity able to decrease the ROS levels, no changes in Cx43 expression could be observed (Figure 2A,D). However, the results were different in a follow-up study by the same group [66]. This time, the DMSA-coated IO-NPs were supplemented to primary cardiomyocytes seeded on a collagen/Matrigel scaffold ( Figure 2C).…”

Nanomaterials for Cardiac Tissue Engineering

“…Iron oxide nanoparticles also stimulate connexin 43 expression in order to promote co-culture of mesenchymal stem cells and cardiomyoblasts, resulting in increased therapeutic efficacy [104]. Mou et al had similar findings [105]. Thus, iron oxide nanoparticles do have a direct effect on cell signaling and phenotype.…”

Iron Oxide Nanoparticles in Regenerative Medicine and Tissue Engineering

“…By incorporating IONPs into bioengineered porous type I collagen patches to repair damaged myocardium, Mahmoudi et al developed a biodegradable material that could be imaged with MRI and also prevented the growth of Salmonella bacteria in the presence of the embedded NPs. In another work, it was shown that internalization of DMSA-IONPs by cardiac cells into collagen/Matrigel-based 3D engineered cardiac tissues increased biological activity and assembly of gap junctions, enhanced the assembly of electrochemical junctions and decreased adherens junctions and desmosomes [ 273 ].…”