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Fe3O4 nanoparticles enhance the sonodynamic therapy effect of chlorin e6 on glioma U251 cells
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Abstract:
Objective: To explore the synergistic effect of Fe3O4 nanoparticles (PION), as a drug carrier, on enhancing the effect of chlorin e6 (Ce6) in glioma. Methods: PEG-Fe3O4@Ce6 composite nanoparticles (PION@E6) were prepared by high temperature degradation method and phase transfer method, and then verified by hydrated particle size analysis, transmission electron microscopy, colloidal stability analysis and ultraviolet-visible light absorption spectroscopy, etc. CCK-8 method was used to detect the proliferation activity of glioma U251 cells, Flow cytometry was used to detect the apoptosis of the cells, and the DCFH-DA probe method was used to detect the level of reactive oxygen species (ROS) in the cells. Glioma U251 cell transplanted tumor model was constructed on BALB/c-nu nude mice. The retention time of PION@E6 and Ce6 in transplanted tumors was observed with animal fluorescence imaging technology and magnetic resonance imaging (MRI), and the survival and tumor volume on the 28th day in the PION@E6 sonodynamic therapy group and Ce6 sonodynamic therapy group were compared. Results: Transmission electron microscopy and hydrated particle size analysis showed that the core particle size of PION@E6 was 10 nm and the hydrated particle size was (37.86±12.90) nm; colloidal stability analysis showed that PION@E6 had good water solubility and stability; and the absorption spectrum and XRD atlas showed that Ce6 had been loaded on Fe3O4 nanoparticles. Compared with the Ce6 sonodynamic group, the proliferation activity of U251 cells in the PION@E6 sonodynamic group was significantly decreased (P<0.05)， the apoptosis rate was significantly increased (all P<0.05)，and the level of ROS in the cells was significantly increased (P<0.05). In vivo experiments on nude mice bearing glioma U251 cell transplanted tumors showed that compared with Ce6 sonodynamic therapy group, the retention time of Ce6 in the transplanted tumor tissues of the PION@E6 sonodynamic therapy group was significantly prolonged (P<0.05)，the number of survived nude mice was significant increased, and the transplanted tumor volume was significantly reduced (P<0.01). Conclusion: Fe3O4 nanoparticles have a significant synergistic effect on Ce6-mediated sonodynamic therapy of glioma U251 cells.
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Project Supported:
Project supported by the National Natural Science Foundation of China (No.32060228), the Natural Science Foundation of Guangxi (No.2017GXNSFAA198112, No.2019GXNSFAA245077), the Innovation Program of Postgraduate Education in Guangxi (No.YCSW2019214, No.YCSW2020225), and the Key Laboratory of Brain and Cognitive Neuroscience Open Project of Guangxi (No.GKLBCN-20200108-02)
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