Toxicity And Biological Effect Of Radiation Investigation Of TiO₂ Nanoparticles

Titanium dioxide (TiO2) nanoparticles had received attentions in photodynamic therapy due to unique electronic structure and high surface activity. However, it is still not clear about the toxicity and biological effect of radiation. Herein, toxicity of TiO2 nanoparticles, including in vitro and in vivo toxicity, was systematically evaluated. Meanwhile, the biological effect of radiation for sub-lethal and lethal dose of TiO2 nanoparticles on mice was evaluated.In vitro toxicity of TiO2 was evaluated by blood stability and MTT. In the work of stability, we found that TiO2 can achieve a dynamic equilibrium after 2 hours, and the absorbance value finally reached a steady level. MTT showed there is a good relationship between the survival rate and concentration in 48 hours. And we can concluded that the higher the concentration, the greater the toxicity in the period of 48 hours. As for 24h, there is uncertain relationship, nevertheless in the range of 0.06 mg/mL-1 mg/mL, revealing a negative correlation.In our work, the experimental mice received 200 μL of TiO2 solution at a dose of 1 mg/mL by intraperitoneal injection. The toxicity of TiO2 was evaluated by immune indexes, body weight change, biodistribution, hematology, biochemistry and histopathology. We found that TiO2 prefer to stay in liver. And some damages of liver were found from the significant differences of AST, ALT. However, the normal working order of kidney was observed by the insignificant differences in CREA and BUN.Next, the biological effect of radiation of TiO2 nanoparticles for sub-lethal dose was evaluated.The experimental mice were treated with 1 mg/mL,2 mg/mL and 4 mg/mL TiO2 nanoparticles respectively. Subsequently, they received whole body radiation of 6.5 Gy γ-ray. The white blood cell (WBC), blood platelet (PLT), hemoglobin (HGB),bone marrow nucleated cells (BMNC),bone marrow DNA were counted to access the biological effect of radiation for TiO2 nanoparticles. Some radioprotection effects were discovered from above concentrations. However, the optimal biological effect of radiation was detected from 4 mg/mL in the period of 8 days.The biological effect of radiation and mechanism for TiO2 nanoparticles to 7.5 Gy lethal dose was also explored. Survival during 30 days and change of WBC、RBC、PLT、 HGB were recorded. The mice injected 2 mg/mL TiO2 nanoparticles presented the better survival rate, and survival time can be extended after injecting 1 mg/mL TiO2 compared to the control mice in the early days of irradiation. Meanwhile, WBC、RBC、PLT、HGB showed the minimum in 7 day, and we concluded that mice suffered the worst damage in 7 day. Then, the indicators of blood gradually recover, and reached a normal state in 30 day.Finally, superoxide dismutase (SOD), malonaldehyde (MDA) of liver and lung were counted to explore the mechanism of biological effect of radiation. And we found TiO2 nanopaticles can improve oxidation resistance to play the role of radioprotection.