Labeling mesenchymal cells with DMSA-coated gold and iron oxide nanoparticles: assessment of biocompatibility and potential applications

Abstract

BackgroundNanoparticles’ unique features have been highly explored in cellular therapies. However, nanoparticles can be cytotoxic. The cytotoxicity can be overcome by coating the nanoparticles with an appropriated surface modification. Nanoparticle coating influences biocompatibility between nanoparticles and cells and may affect some cell properties. Here, we evaluated the biocompatibility of gold and maghemite nanoparticles functionalized with 2,3-dimercaptosuccinic acid (DMSA), Au-DMSA and γ-Fe2O3-DMSA respectively, with human mesenchymal stem cells. Also, we tested these nanoparticles as tracers for mesenchymal stem cells in vivo tracking by computed tomography and as agents for mesenchymal stem cells magnetic targeting.ResultsSignificant cell death was not observed in MTT, Trypan Blue and light microscopy analyses. However, ultra-structural alterations as swollen and degenerated mitochondria, high amounts of myelin figures and structures similar to apoptotic bodies were detected in some mesenchymal stem cells. Au-DMSA and γ-Fe2O3-DMSA labeling did not affect mesenchymal stem cells adipogenesis and osteogenesis differentiation, proliferation rates or lymphocyte suppression capability. The uptake measurements indicated that both inorganic nanoparticles were well uptaken by mesenchymal stem cells. However, Au-DMSA could not be detected in microtomograph after being incorporated by mesenchymal stem cells. γ-Fe2O3-DMSA labeled cells were magnetically responsive in vitro and after infused in vivo in an experimental model of lung silicosis.ConclusionIn terms of biocompatibility, the use of γ-Fe2O3-DMSA and Au-DMSA as tracers for mesenchymal stem cells was assured. However, Au-DMSA shown to be not suitable for visualization and tracking of these cells in vivo by standard computed microtomography. Otherwise, γ-Fe2O3-DMSA shows to be a promising agent for mesenchymal stem cells magnetic targeting.

New perspectives in nanotherapeutics for chronic respiratory diseases

“…In this context, one promising medical application of nanomaterials is the use of inorganic NPs within mesenchymal stromal cell (MSC)-based therapies. Nanomaterials have facilitated not only the acquisition of knowledge of stem cell biology but also allowed the development of new approaches that have enhanced their homing, survival, and biological effects (Silva et al 2016). Silva et al (2016) magnetized MSCs with iron oxide NPs, administered these cells through the jugular vein of silicotic mice, and exposed the animals to a localized magnetic field around the thorax.…”

“…Nanomaterials have facilitated not only the acquisition of knowledge of stem cell biology but also allowed the development of new approaches that have enhanced their homing, survival, and biological effects (Silva et al 2016). Silva et al (2016) magnetized MSCs with iron oxide NPs, administered these cells through the jugular vein of silicotic mice, and exposed the animals to a localized magnetic field around the thorax. The authors found that NPs were able to act as good agents for magnetic targeting of MSCs to the site of injury, resulting in increased cell retention in lung parenchyma and histologic improvement.…”

In Vitro Safety and Quality of Magnetically Labeled Human Mesenchymal Stem Cells Preparation for Cartilage Repair

“…15,16 Iron oxide nanoparticles have been widely reported to produce highly reactive hydroxyl radicals. 17 These radicals and the subsequent oxidative stress are considered biotoxic and have the ability to inhibit chondrogenic differentiation. [18][19][20][21] In this study, the concentration of ferucarbotran necessary to inhibit the chondrogenic differentiation of MSCs varied across donors, probably due to the variation in the amount of intracellularly incorporated iron among the donors.…”

Physicochemical Properties of Magnetic Nanoparticles: Implications for Biomedical Applications In Vitro and In Vivo

“…Other coatings, namely DMSA [37,38], poly(L-lactic acid) [39], citrate [40], oleic acid [41], or oleate [42], and their derivatives, were only used in a few studies, and their biological effects and properties are poorly studied.…”