Study of Killing Effects of A375 Melanoma Cells Treated by Low Intensity Nanosecond Pulsed Electric Fields Combined with Targeted Gold Nanorods
Mi Yan1, Liu Quan1, Li Pan1, Yang Qiyu2, Tang Junying2
1. State Key Laboratory of Power Transmission Equipment & System Security and New Technology Chongqing University Chongqing 400030 China; 2. First Affiliated Hospital Chongqing Medical Science University Chongqing 400016 China
Abstract:To improve the electrical safety associated with nanosecond pulsed electric fields (nsPEFs) in tumor treatment, for the first time, the killing effects of low-intensity nsPEFs combined with folic acid (FA) modified gold nanorods on A375 melanoma cells were investigated. The surface of polyethylene glycol-gold nanorods (GNR-PEG) was modified by folic acid (GNR-PEG-FA) to target A375 melanoma cells, and the binding efficacy was observed by dark field microscopy. After determining the safe concentrations of GNR-PEG and GNR-PEG-FA, the effects of the combined treatment on cell viability and apoptosis were studied by changing electric field strengths (2~8kV/cm) and pulse numbers (15~260). It is found that the combination of low-intensity nsPEFs and GNR-PEG-FA shows the best antitumor efficacy, resulting in lower percentages of viable cells and higher percentages of apoptosis at lower electric field strengths and fewer pulses. This combined treatment enhances the killing effects of A375 melanoma cells and improves the electrical safety of nsPEFs treatment.
米彦, 刘权, 李盼, 杨骐瑜, 唐均英. 低强度纳秒脉冲电场联合靶向金纳米棒对A375黑色素瘤细胞的杀伤效果研究[J]. 电工技术学报, 2020, 35(12): 2534-2544.
Mi Yan, Liu Quan, Li Pan, Yang Qiyu, Tang Junying. Study of Killing Effects of A375 Melanoma Cells Treated by Low Intensity Nanosecond Pulsed Electric Fields Combined with Targeted Gold Nanorods. Transactions of China Electrotechnical Society, 2020, 35(12): 2534-2544.
[1] Beebe S J, Fox P M, Rec L J, et al.Nanosecond pulsed electric field (nsPEF) effects on cells and tissues: apoptosis induction and tumor growth inhibition[J]. IEEE Transactions on Plasma Science, 2002, 30(1): 286-292. [2] 米彦, 彭文成, 芮少琴, 等. 高频纳秒脉冲串作用下皮肤肿瘤热效应的多参数有限元仿真与实验[J]. 电工技术学报, 2017, 32(22): 264-274. Mi Yan, Peng Wencheng, Rui Shaoqin, et al.Thermal effects in skin tumor exposed to high-frequency nanosecond pulse bursts: multi-parametric finite element simulation and experiment[J]. Transactions of China Electrotechnical Society, 2017, 32(22): 264-274. [3] Zhu Shijin, Kisiel W, Lu Yangjing, et al.Tumor angiogenesis therapy using targeted delivery of paclitaxel to the vasculature of breast cancer metastases[J]. Journal of Drug Delivery, 2014(1): 1-12. [4] Buescher E S, Schoenbach K H.Effects of submicrosecond, high intensity pulsed electric fields on living cells-intracellular electromanipulation[J]. IEEE Transactions on Dielectrics and Electrical Insulation, 2003, 10(5): 788-794. [5] 吴子剑, 王晨, 张明艳, 等. 环氧树脂纳米复合材料界面及其对电性能影响分析[J]. 电工技术学报, 2018, 33(16): 3897-3905. Wu Zijian, Wang Chen, Zhang Mingyan, et al.Interface of epoey resin composites, and its influence on electrical performance[J]. Transactions of China Electrotechnical Society, 2018, 33(16): 3897-3905. [6] Qiu Hao, Joshi R P, Pradhan A.Simulation of nanoparticle based enhancement of cellular electroporation for biomedical applications[J]. Journal of Applied Physics, 2014, 116(18): 184701. [7] Rolong A, Prokop K J, Davalos R V.Impact of the use of nanoparticles on electric field distribution during irreversible electroporation treatments: can the lesion be enhanced beyond IRE margin[C]//6th European Conference of the International Federation for Medical and Biological Engineering, Dubrovnik, 2015: 44-54. [8] Huang Shuyang, Deshmukh H, Rajagopalan K K, et al.Gold nanoparticles electroporation enhanced polyplex delivery to mammalian cells[J]. Electrophoresis, 2014, 35(12-13): 1837-1845. [9] Tiwari P K, Soo Lee Y.Gene delivery in conjunction with gold nanoparticle and tumor treating electric field[J]. Journal of Applied Physics, 2013, 114(5): 054902. [10] Aitziber B.Molecular mechanism implicated in pemetrexed-induced apoptosis in human melanoma cells[J]. Molecular Cancer, 2012, 11(1): 25-40. [11] Luis S, Montenegro M F, Cabezas H J, et al.The critical role of alpha-folate receptor in the resistance of melanoma to methotrexate[J]. Pigment Cell & Melanoma Research, 2009, 22(5): 588-600. [12] Mi Yan, Wan Hui, Bian Changhao, et al.An MMCbased modular unipolar/bipolar high-voltage nanosecond pulse generator with adjustable rise/fall time[J]. IEEE Transactions on Dielectrics and Electrical Insulation, 2019, 26(2): 515-522. [13] Niidome T, Yamagata M, Okamoto Y, et al.PEGmodified gold nanorods with a stealth character for in vivo applications[J]. Journal of Controlled Release, 2006, 114(3): 343-347. [14] Li Zhibin, Tang Siying, Wang Beike, et al.Metabolizable small gold nanorods: size-dependent cytotoxicity, cell uptake and in vivo biodistribution[J]. ACS Biomaterials Science & Engineering, 2016, 2(5): 789-797. [15] Selvaraj K, Prasad R, Agawane S, et al.In vivo examination of folic acid-conjugated gold-silica nanohybrids as contrast agents for localized tumor diagnosis and bio-distribution[J]. Bioconjugate Chemistry, 2018, 29(1): 4012-4019. [16] Kopwitthaya A, Yong K T, Hu Rui, et al.Biocompatible pegylated gold nanorods as colored contrast agents for targeted in vivo cancer applications[J]. Nanotechnology, 2010, 21(31): 315101. [17] Arnida, Malugin A, Ghandehari H. Cellular uptake and toxicity of gold nanoparticles in prostate cancer cells: a comparative study of rods and spheres[J]. Journal of Applied Toxicology, 2010, 30(3): 212-217. [18] Freeman S A, Wang M A, Weaver J C.Theory of electroporation of planar bilayer membranes: predictions of the aqueous area, change in capacitance and pore-pore separation[J]. Biophysical Journal, 1994, 67(1): 42-56. [19] 姚陈果, 吕彦鹏, 赵亚军, 等. 基于能量概率与微孔力模型的脉冲电场对细胞电穿孔动态过程的仿真分析[J]. 电工技术学报, 2016, 31(23): 141-149. Yao Chenguo, Lü Yanpeng, Zhao Yajun, et al.Simulation analysis on dynamic process of electroporation by the model based on energy probability and pore force in cell exposed to pulsed electric field[J]. Transactions of China Electrotechnical Society, 2016, 31(23): 141-149. [20] Debruin K A, Krassowska W.Modeling electroporation in a single cell effects of field strength and rest potential[J]. Biophysical Journal, 1999, 77(3): 1213-24. [21] Rojas C, Jose A, Correa D M A, et al. Enhanced introduction of gold nanoparticles into vital acidothiobacillus ferrooxidans by carbon nanotube-based microwave electroporation[J]. Nano Letters, 2004, 4(5): 985-988. [22] Aude S, Isebelle L, Michael L, et al.Cell membrane permeabilization by 12-ns electric pulses: not a purely dielectric, but a charge-dependent phenomenon[J]. Bioelectrochemistry, 2015, 106: 369-378. [23] Alexander V A, Alexander N S, Igor V M, et al.Activity of 2-aryl-2-(3-indolyl) acetohydroxamates against drug-resistant cancer cells[J]. Journal of Medicinal Chemistry, 2015, 58(5): 2206-2220. [24] Schoenbach K H, Hargrave B, Joshi R P, et al.Bioelectric effects of intense nanosecond pulses[J]. IEEE Transactions on Dielectrics and Electrical Insulation, 2007, 14(5): 1088-1109. [25] Schoenbach K H, Beebe S J, Buescher E S.Intracellular effect of ultrashort electrical pulses[J]. Bioelectromagnetics, 2010, 22(6): 440-448. [26] Sundararajan R.Nanosecond electroporation: another look[J]. Molecular Biotechnology, 2009, 41(1): 69-82. [27] 刘红梅, 姚陈果, 董守龙, 等. 基于测量信号的不可逆电穿孔动态过程数值模拟及分析[J]. 电工技术学报, 2019, 34(18): 3732-3740. Liu Hongmei, Yao Chenguo, Dong Shoulong, et al.Dynamic numerical modeling and analyzing on the process of irreversible electroparation based on measurement signal[J]. Transactions of China Electrotechnical Society, 2019, 34(18): 3732-3740. [28] 米彦, 徐进, 刘洪亮, 等. 基于网格传输网络模型的高频纳秒脉冲串作用下单细胞穿孔特性仿真[J]. 电工技术学报, 2018, 33(18): 4217-4230. Mi Yan, Xu Jin, Liu Hongliang, et al.Simulation of performance features in a single-cell system exposed to high-frequency nanosecond pulsed bursts based on mesh transport network model[J]. Transactions of China Electrotechnical Society, 2018, 33(18): 4217-4230. [29] 米彦, 李盼, 刘权, 等. 纳秒脉冲电场联合多壁碳纳米管对皮肤癌细胞活性的剂量效应研究[J]. 电工技术学报, 2019, 34(22): 4849-4857. Mi Yan, Li Pan, Liu Quan, et al.Dose effect of the activity of skin cancer cells treated by nanosecond pulsed electric field combined with multi-walled carbon nanotubes[J]. Transactions of China Electrotechnical Society, 2019, 34(22): 4849-4857. [30] Janja D, Janja V, SanCar J, et al. Connecting the in vitro and in vivo experiments in electrochemotherapya feasibility study modeling cisplatin transport in mouse melanoma using the dual-porosity model[J]. Journal of Controlled Release, 2018, 286: 33-45.