基于Cole-Cole模型评价纳米二氧化钛的细胞毒性作用

Evaluation of Cytotoxicity of Nano Titanium Dioxide Based on Cole-Cole Model

利用Cole-Cole模型评价不同剂量纳米二氧化钛(Nano-TiO_2)的细胞毒性作用,并探讨电生理机制。150和300 mg/L的Nano-TiO_2悬液作用人胃癌MGC803细胞24 h后,制备成细胞悬浮液。在1 k Hz^100 MHz范围,采用Agilent 4294A精密阻抗分析仪测量了人胃癌MGC803细胞悬浮液电阻抗的幅值和相位角,经电阻抗频谱和Nyquist图的曲线拟合的残差分析,建立Cole-Cole模型参数,评估Nano-TiO_2对MGC803细胞导电性能的影响。结果表明,150和300 mg/L的Nano-TiO_2引起第一电阻抗增量(ΔZ1)分别减少18.18%(P<0.001)和39.39%(P<0.001),第二电阻抗增量(ΔZ2)分别减少6.56%(P<0.001)、8.2%(P<0.001),降低了MGC803细胞膜及其核膜的电阻,增加了其导电性能;第一特征频率(fC1)分别增加19.74%(P<0.001)和29.67%(P<0.001),第二特征频率(fC2)分别增加6.28%(P<0.001)、23.43%(P<0.001);第一散射角(β1)分别降低1.35%(P>0.05)和2.70%(P<0.05)。ColeCole模型可评价Nano-TiO_2的细胞毒性作用并解释其电生理机制,为纳米颗粒的细胞毒理研究提供一种电特性方法。

The aim of this work is to evaluate the cytotoxicity of titanium dioxide nanoparticles （ Nano-TiO2） at different doses based on Cole-Cole model and explore the electrophysiological mechanism. The haman gastric cancer cell MGC803 was exposed to 150 mg/L and 300 mg/L Nano-TiO2 suspension for 24 h. The amplitude and phase angle of the impedance of human gastric cancer MGC803 cell suspension were measured by 4294A Agilent precision impedance analyzer in the range of 1 kHz - 100 MHz. Based on the residual analysis of the curve fitting of the electrical impedance spectroscopy and the Nyquist plot, the parameters of the Cole-Cole model were established, and the effect of Nano-TiO2 on the conductivity of MGC803 cells was evaluated based on the Cole-Cole model. Results showed that 150 mg/L and 300 mg/L of Nano-TiO2 induced the first impedance increment （△Z1） decreased 18.18% （P 〈 0. 001 ） and 39.39% （P 〈 0. 001 ） respectively, the second impedance increment （ △Z2 ） decreased 6.56% （ P 〈 0. 001 ） and 8.2% （ P 〈 0. 001 ） respectively, and reduced the resistance of cellular membrane and nuclear membrane of MGC803 cells, increased its conductivity. The first characteristic frequency （fc1） was increased by 19. 74% （P 〈 0. 001） and 29.67% （P 〈0. 001） respectively, and second characteristic frequency （fc2） was increased by 6.28% （P 〈 0. 001 ） and 23.43% （P 〈 0. 001 ） respectively. The first dispersion angle （β1） was reduced by 1.35% （P 〉 0.05） and 2.70% （P 〈 0.05） , respectively. The Cole-Cole model can be applied to evaluate the role of Nano-TiO2 and explain its eleetrophysiological mechanism, providing a method for the study of cytotoxicity of nanoparticles.