| Mesenchymal stem cells (MSCs) are broadly accepted in tissue repair and regeneration for its peculiar characteristics. Nanoparticles (NPs) are often used together with MSCs for multiple purposes such as tissue repair and regeneration, labelling and tracking, drug delivery and gene delivery. Moreover, the metal oxide NPs are mostly preferred for such applications due to comparatively enhanced properties. It is widely known that the cellular uptake and endocytosis of NPs can alter cell function and even affect the differentiation potential of MSCs. This impact generally depends on the NPs characteristics like their composition, size/shape, protein corona and surface chemistry. Among these parameters, the surface chemistry of NPs has significant effect on MSC differentiation, but it is not thoroughly studied.In the first project, two kinds of iron oxide nanoparticles with different surface chemistry, i.e. one in its pristine form (P-NPs) without extra capping molecules and the other coated with citrate (C-NPs), with a similar size,～10 nm measured by transmission electron microscopy (TEM) were used. Both P-NPs and C-NPs aggregated to some extent in water, with hydrodynamic diameters of 211.4 ± 29 and 128.6 ± 6.3 nm, and surface zeta potential of +23.5 ± 0.3 and -49.6 ± 0.5 mV. respectively. However, both NPs further aggregated to a similar extent with hydrodynamic diameters of 260 ±5.5 and 214 ± 6.4 nm and slightly negative surface charge (～-10 mV) in cell differentiation media. On incubation of rat MSCs with NPs for 14 d, both NPs showed similar cell uptake kinetics and final intracellular iron content, and minimal cytotoxicity at a concentration below 100 μg/mL. The adipogenic differentiation potential of MSCs was unaltered regardless of the NPs types, and the P-NPs did not have obvious impact on the osteogenic differentiation potential of MSCs either. The osteogenic differentiation potential of the MSCs was significantly impaired on incubation with the C-NPs, as evidenced by significantly reduced expressions of osteogenic markers, namely collagen type Ⅰ (COL), osteocalcein (OCN) and calcium deposition. The uptake of C-NPs and surface-anchored citrate molecules were found to have a synergistic role.In the second project, four different kinds of TiO2 nanorods (TiO2NRds), one in its pristine form (Core) and the others modified with carboxyl (-COOH), amine (-NH2) and poly(ethylene glycol) (PEG) functional groups on their surface having similar length (50 to 100 nm) and width (8nm) measured by TEM were used. The TiO2NRds-Core induced highest toxicity and highest production of reactive oxygen species (ROS). The adipogenic differentiation was comparatively unaffected. Calcium deposition was significantly reduced by 21.38%(TiO2 NRds-Core),22.47%(TiO2NRds-COOH), 14.85%(TiO2 NRds-NH2) and 11.66%(TiO2 NRds-PEG) at 10μg/mL concentration with respect to control depicting surface chemistry dependent influence on osteogenic differentiation of MSCs. The TiO2NRds-COOH impaired osteogenic differentiation to highest extent despite having low uptake, low toxicity and least production of ROS. Thus, the TiO2 NRds can impose surface chemistry dependent cellular uptake, cytotoxicity and differentiation effect on MSCs to some extent. |
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