Effects of gold nanostructures on differentiation of mesenchymal stem cells

Abstract

Nanoparticles are nanocrystals with complex facets and defective structures that do not adopt an idealised shape. Various physicochemical parameters of nanoparticles, such as surface composition, size, and stiffness, can regulate differentiation in mesenchymal stem cells (MSCs), but the influence of shapes with many edges and corner regions has not been investigated. Herein, we investigated the effects of two gold nanostructures modified with 11-mercaptoundecanoic acid, namely gold nanocubes (MUA-AuNCs) and nanooctahedras (MUA-AuNOs), on viability and differentiation in rat bone marrow MSCs (bMSCs). Analysis of cytotoxicity and proliferation demonstrated good biocompatibility, with concentrations <100 μg·mL^-1 not significantly different from untreated controls. Alkaline phosphatase activity and Alizarin Red S staining revealed weaker potential for bMSCs to differentiate into osteoblasts following treatment with both low (5 μg·mL^-1) and high (25 μg·mL^-1) concentrations of the gold nanostructures. By contrast, Oil Red O staining showed that both nanostructures enhanced adipogenic differentiation, and upregulated peroxisome proliferator-activated receptor gamma (PPARγ) and fatty acid binding protein-4 (Fabp4) expression at both mRNA and protein levels. The effects on differentiation were both structure- and dose-dependent; MUA-AuNOs were more effective for enhancing adipogenic differentiation and weakening osteogenic differentiation, possibly due to generating higher levels of reactive oxygen species (ROS). These findings lay the foundation for using these nanoparticles as ex vivo labels in MSC-based imaging and therapy.

Keywords: Cytotoxicity; Differentiation; Gold nanostructures; Mesenchymal stem cells.