Cytocompatible manganese dioxide-based hydrogel nanoreactors for MRI imaging

Abstract

The application of nanoparticles in magnetic resonance imaging (MRI) has been greatly increasing, due to their advantageous properties such as nanoscale dimension and tuneability. In this context, manganese (Mn2+)-based nanoparticles have been greatly investigated, due to their valuable use as a contrast agent, improving signal intensity and specificity in MRI (manganese-enhanced MRI, MEMRI). Additionally, Mn2+ can act as scavengers of reactive oxygen species (ROS), commonly present in the inflammatory processes of neurodegenerative diseases. The aim of the present study was to develop nanoreactors, which can be used as contrast-agent in MEMRI. Several blends of methacrylated gellan gum (GG-MA) and hyaluronic acid (HA) were embedded with different types of manganese dioxide (MnO2) nanoparticles and further physico-chemically characterized. Dynamic light scattering, scanning electron microscopy, water uptake and degradation studies were performed. In vitro cytotoxicity of the different formulations was also evaluated using an immortalized rat fibroblast cell line L929, up to 72 h of culturing. Synthesized nanoparticles were obtained with an average size of 70 nm and round-shaped morphology. The stability of the different formulations of hydrogels was not affected by nanoparticles' concentration or HA ratio. The presence of synthesized MnO2 (MnO2_S) nanoparticles reduced hydrogels' cytocompatibility, whereas the commercially available type 1 (MnO2_C1) nanoparticles were less toxic to cells. Additionally, cell proliferation and viability were enhanced when a lower content of HA was present. Higher concentrations (75 and 100 ng/mL) of MnO2_S and MnO2_C1 nanoparticles did not negatively affected cell viability, whereas the opposite effect was observed for the commercial type 2 (MnO2_C2) nanoparticles. Further studies are required to evaluate the potential application of the most promising nanoreactors' formulations for combined application in MEMRI and as ROS scavengers.