Fabrication of multifunctional bismuth-doped iron nanoparticle and its radiotherapy sensitization in glioblastoma / 中国组织工程研究

ABSTRACT

BACKGROUND:Bismth-doped iron nanoparticles modified by hyaluronic acid (HA-BiIOPs) not only act as an effective MRI contrast agent, but also as a radiotherapy sensitizer.OBJECTIVE:To fabricate the HA-BiIOPs and to observe its effect to enhance the radiosensitivity of glioblastoma cells U87MG under X-ray radiation.METHODS:HA-BiIOPs were synthesized using hydrothermal polyol method. (1) Cytotoxicity A cytotoxicity test was carried out on U87MG cells and rat vascular smooth muscle cells (VSMCs). Cell proliferation rate of two kinds of cells cultured with different concentrations of HA-BiIOPs (0, 12.5, 25, 50, 100, 200, 400 mg/L) at 24 hours after culture were determined by cell counting kit-8 assay. (2) Histological analysis: ICR mice were sacrificed after intravenous injection of HA-BiIOPs, and pathological changes of mouse visceral organs were observed under an optical microscope. (3) Cellular uptake The HA-BiIOPs after entered into the cytoplasm were observed by Prussian blue staining. (4) Radiosensitization test U87MG cells at Logarithmic growth stage were cultured in culture medium as control group, subjected to X-ray irradiation (0, 3, 6, 9 Gy) as radiotherapy group, cultured in HA-BiIOPs (0, 12.5, 25, 50, 100, 200 and 400 mg/L) as HA-BiIOPs group or subjected to HA-BiIOPs culture plus X-ray irradiation as combined therapy group. Then, the cell proliferation rate and cloning efficiency were measured at 24 hours after treatment.RESULTS AND CONCLUSION:(1) The HA-BiIOPs at different concentrations were non-cytotoxic for VSMC and U87MG cells. (2) After intravenous injection of HA-BiIOPs, there was no obvious toxicity to the mouse susceptible organs. (3) After 6 hours of culture, the HA-BiIOPs could be internalized by U87MG cells. (4) The proliferation rate of U87 cells was negatively correlated with the concentration of HA-BiIOPs (0-200 mg/L) and X-ray dose (0-9 Gy). Especialy, the combination of 6 Gy X-ray irradiation with 200 mg/L HA-BiIOPs dramatically decreased the cell viability that was decreased to (41±7)%. In the combined therapy group with 6 Gy X-ray and 100 mg/L HA-BiIOPs, the cells proliferation rate was significantly lower than that in the control and radiotherapy groups (P < 0.05). These results indicate that HA-BiIOPs have a radiosensitizative effect on glioblastoma cells U87MG.