Effects of 2,3-dimercaptosuccinic acid modified Fe2O3 nanoparticles on microstructure and biological activity of cardiomyocytes

Abstract

Iron oxide nanoparticles (IRONs) have been widely applied in clinical magnetic resonance imaging and in vitro cardiac tissue engineering. However, the underlying effects of IRONs on the microstructures and biological activity of cardiomyocytes remain a controversial issue. In this study, IRONs were modified with 2,3-dimercaptosuccinic acid (DMSA-IRONs) to increase the hydrophobicity. The effects of DMSA-IRONs on the microstructures and biological activity of cardiomyocytes were systematically investigated. DMSA-IRONs were internalized by cardiomyocytes and mainly distributed in the cytoplasm in a dose-dependent manner. Live/dead assay and MTT assay demonstrated that DMSA-IRONs did not affect the survival of cardiomyocytes. The distribution pattern of F-actin and cell shape were also not changed by the incubation of DMSA-IRONs. Further investigations of the mechanism proved that DMSA-IRONs did not interfere with the formation of cell adherens junctions, gap junctions and intracellular Ca²⁺ transients of cardiomyocytes. However, the intracellular reactive oxygen species (ROS) concentration in cardiomyocytes with incubation of DMSA-IRONs was significantly reduced due to its peroxidase-like activity. In conclusion, DMSA-IRONs are of good biocompatibility and potentially beneficial for cardiomyocytes by decreasing the intracellular ROS. The study here provides a basic investigation of the DMSA-IRONs application in clinical cell-imaging and cardiac disease therapy.