NaGdF4:Yb/Er nanoparticles of different sizes for tracking mesenchymal stem cells and their effects on cell differentiation.

Mesenchymal stem cells (MSCs) hold great promise in the field of regenerative medicine, and great effort goes into investigating the mechanisms underlying their therapeutic effects. These investigations necessitate the development of sensitive and reliable methods of tracking stem cells. As the unique physicochemical properties of β-NaGdF4:Yb/Er upconversion nanoparticles make them highly efficient fluorescent probes, they could be utilized to track stem cells through bio-imaging. However, their biocompatibility constitutes a major challenge to their use in biomedical applications. In this paper, we prepared ligand-free spherical β- NaGdF4:Yb/Er nanoparticles of two different sizes (~15 and ~30 nm in diameter) and investigated their internalization into rat bone marrow-derived MSCs (rBMSCs), as well as their effects on cell proliferation, osteogenic and adipogenic differentiation. Even though particles of both sizes were efficiently taken up by the cells, the larger particles had a stronger fluorescence intensity but their proliferation was not significantly affected; this makes them superior for cell imaging. Analysis of multiple markers revealed that the nanoparticles, especially the larger ones, promoted the process of osteogenic differentiation. In contrast, adipogenesis was slightly hindered by the larger particles, whereas the smaller ones did not affect the process. As a whole, this study suggests that ligand-free spherical β-NaGdF4:Yb/Er particles of appropriate size are compatible with stem cell proliferation and differentiation, which makes them promising agents for biomedical applications.