基于微秒脉冲调制高频纳秒脉冲电场诱导凋亡并激发不可逆电穿孔效应治疗肿瘤的基础研究

项目名称： 基于微秒脉冲调制高频纳秒脉冲电场诱导凋亡并激发不可逆电穿孔效应治疗肿瘤的基础研究

项目编号： No.51477022

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 电工技术

项目作者： 米彦

作者单位： 重庆大学

项目金额： 90万元

中文摘要： 为解决现有脉冲电场治疗肿瘤技术存在的问题，并同时发挥微秒脉冲电场（μsPEF）的直接杀伤作用和纳秒脉冲电场（nsPEF）的间接调控作用，本项目提出基于微秒脉冲调制高频nsPEF诱导凋亡并激发不可逆电穿孔效应治疗肿瘤的创新思路。建立考虑频率色散效应的肿瘤细胞等效电路模型和肿瘤组织介电模型，通过细胞内外膜跨膜电位理论计算和热效应评估，确定脉冲窗口参数；建立包含细胞核和线粒体的肿瘤细胞微观传输网格模型，在网格等效电路中引入压控电流源，深入研究微秒脉冲调制高频nsPEF的协同穿孔规律和累积穿孔规律；开展离体细胞实验和荷瘤动物实验，研究微秒脉冲调制高频nsPEF诱导凋亡并激发不可逆电穿孔的全面杀伤机理，并验证其有效性与安全性。本项目旨在揭示微秒脉冲调制高频nsPEF治疗肿瘤技术的原理和方法，为最终成功开发拥有自主知识产权的新型医疗设备提供理论基础和实验依据，具有重要的学术价值和良好的临床应用前景。

中文关键词： 纳秒脉冲电场；高频；凋亡；不可逆电穿孔；肿瘤治疗

英文摘要： In order to solve the problems involved in tumor treatment using pulsed electric fields (PEF), this project presented a novel tumor treatment method using high-frequency nanosecond pulsed electric fields (nsPEF) modulated by microsecond pulse based on both apoptosis and irreversible electroporation, also aiming at direct killing effects of microsecond pulsed electric fields (μsPEF) and indirect modulating effects of nsPEF. Firstly, a equivalent circuit model of spherical cell with the consideration of cellular structure dispersion was established and used to calculate transmembrane potentials of plasma membrane and intracellular membrane to obtain the minimum pulse parameters. A dielectric model of tumor tissue was also established and used to assess the thermal effects of this new method to get the maximum pulse parameters. As a result, a range of appropriate pulse parameters for this method was achieved. After that, a transport lattice model of cancer cell with nucleus and mitochondria, introducing a voltage controlled current source into its equivalent circuit, was proposed to thoroughly investigate the regulations of synergistic and cumulative electroporation of cancer cells exposed to the new pulse in this project. Finally, cell experiment in vitro and animal experiment in vivo were carried out to explore the lethal machanisms of cancer cells possibly associated with both apoptosis and irreversible electroporation. The efficacy and safety of this novel method were also verified by these medical experiments. In conclusion, principle and technology of this new method presented in this project would provide theoretical basis and experimental evidence for development of new medical equipment based on high-frequency nsPEF modulated by microsecond pulse with important academic value and good prospects for clinical application.

英文关键词： nanaosecond pulsed electric fields;high-frequency;apoptosis;irreversible electroporation;tumor treatment