电工技术学报  2019, Vol. 34 Issue (22): 4839-4848    DOI: 10.19595/j.cnki.1000-6753.tces.181456
生物电工 |
纳秒脉冲高频透膜效应优先杀伤化疗抗性肿瘤细胞的仿真与实验研究
刘红梅, 董守龙, 宁郡怡, 郑爽, 姚陈果
输配电装备及系统安全与新技术国家重点实验室(重庆大学) 重庆 400044
Simulation and Experimental Study on Preferential Killing of Chemoresistance Tumor Cells Induced by the High-Frequency Permeation Effect of Nanosecond Pulse Field
Liu Hongmei, Dong Shoulong, Ning Junyi, Zheng Shuang, Yao Chenguo
State Key Laboratory of Power Transmission Equipment & System Security and New Technology Chongqing University Chongqing 400044 China
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摘要 为克服当前临床肿瘤治疗的致命屏障——化疗抵抗,同时弥补纳秒脉冲电场(nsPEFs)对化疗抵抗肿瘤细胞诱导的生物电效应研究的空白,该文结合仿真与实验,对nsPEFs的作用特性及对化疗抵抗肿瘤细胞的杀伤效应进行研究。首先,基于有限元平台,建立考虑细胞器的五层介电模型及考虑细胞内外膜穿孔的数值模型,分析nsPEFs的高频透膜特性、内膜电穿孔效应及其受核质比大小的影响规律;其次,以A549及其同源化疗抵抗的A549/R细胞为研究对象,结合荧光探针和流式技术,研究其在nsPEFs作用下内外膜荧光消散情况,并比较A549及A549/R形态学及其对nsPEFs作用的敏感性差异。结果表明,nsPEFs具有高频特性,可高效率作用到细胞内膜,诱导核膜荧光消散,其诱导的内膜穿孔效应与细胞核(核质比)大小呈正相关,对更高核质比的A549/R细胞有更高杀伤效果。研究结果证明,高压nsPEFs可靶向细胞内部并优先杀伤核质比更大的化疗抵抗肿瘤细胞,可为化疗抵抗肿瘤细胞的选择性杀伤提供理论和实验依据,也为nsPEFs作为一种新的物理选择方式,联合其他肿瘤治疗方法实现顽固性肿瘤组织的有效消融奠定基础。
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刘红梅
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郑爽
姚陈果
关键词 纳秒脉冲化疗抵抗电穿孔肿瘤治疗靶向消融选择性内电处理    
Abstract:In order to overcome the barrier of clinical tumor treatment—chemoresistance, and to make up for the blank of bioelectric effect on chemoresistance tumor cells (CRTCs) induced by nanosecond pulse electric fields (nsPEFs), simulations and experiments were combined in this paper. Firstly, based on the finite element platform, a five-layer dielectric model considering organelles and a numerical model considering the electroporation of inner and outer membranes were established. The high-frequency permeation effect, targeting characteristics and the influence from cell nucleus size were analyzed. Then, taking A549 and homologous A549/R as research objects, this paper further studied the fluorescence dissipation of inner/outer membrane under nsPEFs, and compared the differences of the morphology and killing effects between A549 and A549/R based on the fluorescent probe and flow techniques. It is shown that nsPEFs can efficiently target the inner membrane and induce the fluorescence dissipation of the cell nuclear membrane. This intracellular effect is positively correlated with the nucleus size (or nucleo-cytoplasmic ratio, NCR), causing higher killing effect on A549/R with higher NCR. Therefore, high voltage nsPEFs can target inner membrane to priority kill CRTCs. These results provide theoretical and experimental basis for selective killing of the CRTCs, and also lay a foundation for nsPEFs as a new physical selective method, which can be combined with other tumor treatment methods to achieve effective ablation of refractory tumor tissues.
Key wordsNanosecond pulse    chemoresistance    electroporation    tumor treatment    targeted ablation    selectivity    intracellular electromainpulation   
收稿日期: 2018-09-10      出版日期: 2019-11-28
PACS: TM11  
  TM836  
  Q64  
通讯作者: 姚陈果 男,1975年生,教授,博士生导师,研究方向为电气设备在线监测与故障诊断技术、生物医学中的电工新技术及高电压新技术。E-mail: yaochenguo@cqu.edu.cn   
作者简介: 刘红梅 女,1992年生,博士研究生,研究方向为脉冲功率技术及其生物医学应用。E-mail: liuhongmei@cqu.edu.cn
引用本文:   
刘红梅, 董守龙, 宁郡怡, 郑爽, 姚陈果. 纳秒脉冲高频透膜效应优先杀伤化疗抗性肿瘤细胞的仿真与实验研究[J]. 电工技术学报, 2019, 34(22): 4839-4848. Liu Hongmei, Dong Shoulong, Ning Junyi, Zheng Shuang, Yao Chenguo. Simulation and Experimental Study on Preferential Killing of Chemoresistance Tumor Cells Induced by the High-Frequency Permeation Effect of Nanosecond Pulse Field. Transactions of China Electrotechnical Society, 2019, 34(22): 4839-4848.
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