不同表面金屬氧化物納米微粒對干細胞分化行為的影響研究.pdf

1、Mesenchymal stem cells (MSCs)are broadly accepted in tissue repair andregeneration for its peculiar characteristics.Nanoparticles (NPs) are often used togetherwith MSCs for multiple purposes such as tissue repair and reg

2、eneration, labelling andtracking, drug delivery and gene delivery.Moreover, the metal oxide NPs are mostlypreferred for such applications due to comparatively enhanced properties.It is widelyknown that the cellular uptak

3、e and endocytosis of NPs can alter cell function and evenaffect the differentiation potential of MSCs.This impact generally depends on the NPscharacteristics like their composition, size/shape, protein corona and surface

4、 chemistry.Among these parameters, the surface chemistry of NPs has significant effect on MSCdifferentiation, but it is not thoroughly studied.
　　In the first project, two kinds of iron oxide nanoparticles with differ

5、ent surfacechemistry, i.e.one in its pristine form (P-NPs) without extra capping molecules and theother coated with citrate (C-NPs), with a similar size, ～10 nm measured by transmissionelectron microscopy (TEM) were used

6、.Both P-NPs and C-NPs aggregated to someextent in water, with hydrodynamic diameters of 211.4 ± 29 and 128.6 ± 6.3 nm, andsurface zeta potential of +23.5 ± 0.3 and-49.6 ± 0.5 mV, respectively.However, bothNPs further agg

7、regated to a similar extent with hydrodynamic diameters of 260 ± 5.5and 214 ± 6.4 nm and slightly negative surface charge (～-10 mV) in cell differentiationmedia.On incubation of rat MSCs with NPs for 14 d, both NPs showe

8、d similar celluptake kinetics and final intracellular iron content, and minimal cytotoxicity at aconcentration below 100 μg/mL.The adipogenic differentiation potential of MSCs wasunaltered regardless of the NPs types, an

9、d the P-NPs did not have obvious impact onthe osteogenic differentiation potential of MSCs either.The osteogenic differentiationpotential of the MSCs was significantly impaired on incubation with the C-NPs, asevidenced b

10、y significantly reduced expressions ofosteogenic markers, namely collagentype Ⅰ (COL), osteocalcein (OCN) and calcium deposition.The uptake of C-NPs andsurface-anchored citrate molecules were found to have a synergistic

11、role.
　　In the second project, four different kinds of TiO2 nanorods (TiO2NRds), one inits pristine form (Core) and the others modified with carboxyl (-COOH), amine (-NH2)and poly(ethylene glycol) (PEG) functional gro

12、ups on their surface having similarlength (50 to 100 nm) and width (8nm) measured by TEM were used.The TiO2 NRds-Core induced highest toxicity and highest production of reactive oxygen species (ROS).The adipogenic differ

13、entiation was comparatively unaffected.Calcium deposition wassignificantly 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 concentrationwith respect

14、 to control depicting surface chemistry dependent influence on osteogenicdifferentiation of MSCs.The TiO2 NRds-COOH impaired osteogenic differentiation tohighest extent despite having low uptake, low toxicity and least p