Preparation of magnetic nanoparticle Fe3O4@ZIF-8 MOF loaded with tanshinone ⅡA and its effects on proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells
Objective To prepare the magnetic nanoparticle Fe3O4@ZIF-8 MOF(Fe3O4@ZIF-8@Tan ⅡA)loaded with tanshinone ⅡA,and to observe the promoting effects of Fe3O4@ZIF-8@Tan ⅡA on proliferation and osteogenic differ-entiation of bone marrow mesenchymal stem cells(BMSCs).Methods Fe3O4 nanoparticles were surface-modified with zeolite imidazolate skeleton material(ZIF-8),and tanshinone ⅡA(Tan ⅡA)was loaded into magnetic nanoparticle Fe3O4@ZIF-8 MOF and the drug loading and encapsulation rate of Fe3O4@ZIF-8@Tan ⅡA were detected by HPLC,and the drug release rate of Fe3O4@ZIF-8@Tan ⅡA was calculated.BMSCs were divided into four groups after culture in vitro.BMSCs in the control group were added with osteogenic induction solution+complete medium;BMSCs in the free drug group were added with osteogenic induction solution+Tan ⅡA complete medium containing 10.27 µg/mL;BMSCs in the carrier group were added with osteogenic induction solution+Fe3O4@ZIF-8 MOF complete medium containing 100 µg/mL;in the drug loading group,osteogenic induction solution+Fe3O4@ZIF-8@Tan ⅡA complete medium containing 100 µg/mL were added.OD values of cells in each group were detected by MTT method at different time points(1,4,7 d),and ALP activity was detected by alkaline phosphatase(ALP)kit at different time points(1,4 d).Results The average particle size of Fe3O4@ZIF-8@Tan ⅡA was 307.12 nm,the PDI was 0.090,the potential was-40.03 mV;it was almost spherical with rough surface,the specific surface area was 337.32m2/g,the magnetic saturation intensity was about 48 emu/g,and it had good superparamagnetism.The drug loading capacity of Fe3O4@ZIF-8@Tan ⅡA was 10.27%,and the encapsula-tion efficiency was 80.36%.The in vitro release behavior of Fe3O4@ZIF-8@Tan ⅡA was pH-responsive and could acceler-ate the release rate in a stimulated osteoporotic microenvironment.Compared with the control group,OD value of cells in the loading group increased after four days of administration,and OD value of cells in the other three groups increased after 7 days of administration(all P<0.05).Compared with the control group,the ALP activity of cells in the drug loading group was enhanced after 1 day of administration,and the ALP activity of cells in the carrier group and the drug loading group was enhanced after 4 days of administration(all P<0.05).Conclusions Fe3O4@ZIF-8@Tan ⅡA has good drug loading performance,superparamagnetism,high drug loading capacity and encapsulation rate,and can achieve the effect of slow drug release,and improve the shortcomings of Tan ⅡA such as water solubility and poor drug formation.Fe3O4@ZIF-8@Tan ⅡA can synergistically promote the proliferation and differentiation of BMSCs.
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