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冷大气压等离子体（cold atmospheric plasma,CAP）由于其具有“选择性”杀伤癌细胞的效果，被认为是一种极具潜力的癌症治疗手段。然而，CAP对癌细胞的“选择性”杀伤作用相关的物理模型及CAP与癌细胞相互作用的微观机理仍然匮乏。本文采用分子动力学方法模拟了CAP激发电场引起的细胞膜电穿孔（electroporation,EP）效应，并采用伞形采样法计算了ROS（reactive oxygen species,ROS）通过EP形成的不同阶段的孔结构进入细胞内部的自由能剖面。结果表明，相较于正常细胞膜，胆固醇含量较低的癌细胞膜发生EP的电场强度阈值更低，且EP发生时间更快；对于ROS的转运过程而言，由于癌细胞膜胆固醇含量更低，在EP的各个阶段下ROS的自由能势垒更低，因此在EP的各个阶段下，ROS内流的时间均早于正常细胞。本文从分子模拟的角度探索了CAP激发电场作用下EP的形成过程，以及EP的不同阶段中ROS转运的潜在机会，有利于更清楚地阐述CAP“选择性”抗癌作用的微观机理，并为CAP癌症治疗技术、设备和手段的研发提供了重要参考，促进了CAP在临床应用方面的发展。Cold atmospheric plasma (CAP), due to its “selective” anti-cancer effect, is considered to be a highly promising cancer treatment method. However, the physical theoretical explanation about the effect and the microscopic interactive mechanisms between CAP and tumors are still lacking. In this work, the CAP-induced electric field-caused electroporation (EP) processes of the cell membrane are modeled based on molecular dynamics. Additionally, the umbrella sampling method was carried out to compute the free energy profile of the intracellular permeation processes of the reactive oxygen species (ROS) through EP-formed pore-like structures at different EP stages. Comparative results showed that: 1) Cancer cell membranes with lower cholesterol components showed lower EP-generation threshold and faster EP-formation; 2) Lower free-energy barrier and earlier occurrence of free-energy barrier reduction are shown in all EP stages in cancer cell membrane. The Above results explain the difference between cancer cells and normal cells when affected by CAP. Our work thoroughly explores the formation of CAP-induced EP and the transport of ROS through EP-formed pore-like structures, which contributes to a more lucid understanding of the microscopic mechanisms of the “selective” anti-cancer effect of CAP. And provides crucial references for the development of CAP-based cancer treatment methodologies, technologies, and devices, thereby facilitating the translation of CAP into clinical applications.
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Keywords:
- Cold Atmospheric Plasma /
- Electric Field /
- Cell Membrane Electroporation /
- Molecular Dynamics
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[1] Lu X P, Luo J Y, Nie L L, Liu D W, Zhang G J, Liu D X, Shao T, Fang Z, Jin S S, Zhao Y J, Zhang Y T, Zou L, Wang X L, Li H P, Zhang Y, Liu D P, Yang D Z, Chen Z T, Huang Q, Chen C, Wu S Q, Liu Q J, Pei X K, Yan X, Cheng H, Xiong Q, Shi Q, Song K, Cao Y G, Chen H X, Feng A P, Xia Y M, Bai F, Yang C J, Yang R G, He G Y 2024High Voltage Engineering 503555(卢新培, 罗婧怡, 聂兰兰, 刘大伟, 张冠军, 刘定新, 邵涛, 方志, 金珊珊, 赵亚军, 张远涛, 邹亮, 王晓龙, 李和平, 张宇, 刘东平, 杨德正, 陈支通, 黄青, 程诚, 吴淑群, 刘巧珏, 裴学凯, 闫旭, 程鹤, 熊青, 石琦, 宋珂, 曹颖光, 陈宏翔, 冯爱平, 夏育民, 白帆, 杨春俊, 杨润功, 何光源2024 高电压技术 50 3555)
[2] Chen X, Wang X, Zhang B, Yuan M, Yang S 2023Chinese Phys. B 32115201
[3] Fang J, Zhang Y, Lu C, Gu L, Xu S, Guo Y, Shi J 2024Chinese Phys. B 33 015201
[4] Xu H, Gao J, Jia P, Ran J, Chen J, Li J 2024Chinese Phys. B 33 015205
[5] Schleusser S, Schulz L, Song J, Deichmann H, Griesmann A-C, Stang F H, Mailaender P, Kraemer R, Kleemann M, Kisch T 2022 Microcirculation 29 e12754
[6] Filipic A, Gutierrez-Aguirre I, Primc G, Mozetic M, Dobnik D 2020 Trends in Biotechnology 38 1278
[7] Nguyen L, Lu P, Boehm D, Bourke P, Gilmore B F, Hickok N J, Freeman T A 2019 Biol. Chem. 400 77
[8] Zhou R, Zhang X, Zong Z, Li J, Yang Z, Liu D, Yang S 2015Chinese Phys. B 24 085201
[9] Borges A C, Kostov K G, Pessoa R S, de Abreu G M A, Lima G d M G, Figueira L W, Koga-Ito C Y 2021 Appl. Sci. 11 1975
[10] von Woedtke T, Laroussi M, Gherardi M 2022 Plasma Sources Sci.T. 31 054002
[11] Min T, Xie X, Ren K, Sun T, Wang H, Dang C, Zhang H 2022 Frontiers in Medicine 9 884887
[12] Yan D, Horkowitz A, Wang Q, Keidar M 2021 Plasma Processes Polym. 18 e2100020
[13] Yan D, Sherman J H, Keidar M 2017 Oncotarget 8 15977
[14] Yao C G 2018High Voltage Engineering 44 248(姚陈果2018 高电压技术 44 248)
[15] Graves D B 2012 J. Phys. D Appl. Phys. 45 263001
[16] Haberl S, Miklavcic D, Sersa G, Frey W, Rubinsky B 2013 IEEE Electr. Insul. M 29 29
[17] Ruzgys P, Novickij V, Novickij J, Satkauskas S 2019 Bioelectrochemistry 127 87
[18] Wu E, Nie L, Liu D, Lu X, Ostrikov K 2023 Free Radical Bio. Med. 198 109
[19] Szlasa W, Kielbik A, Szewczyk A, Rembialkowska N, Novickij V, Tarek M, Saczko J, Kulbacka J 2021 Molecules 26 154
[20] Sun Y K, Guo L H, Wang K C, Wang S M, Gong Y B 2021Acta Phys. Sin. 70 327(孙远昆, 郭良浩, 王凯程, 王少萌, 宫玉彬2021 70 327)
[21] Xing R F, Chen M, Li R Y, Li S Q, Zhang R, Hu X C 2024Acta Phys. Sin. 73 295(邢人芳, 陈明, 李芮羽, 李淑倩, 张瑞, 胡笑钏2024 73 295)
[22] Hu X, Jin X, Xing R, Liu Y, Feng Y, Lyu Y, Zhang R 2023 Results Phys. 51 106621
[23] Yang S, Zhao T, Zou L, Wang X, Zhang Y 2019 Phys. Plasmas 26 083504
[24] Zhao X, Ding W, Wang H, Wang Y, Liu Y, Li Y, Liu C 2023 J. Chem. Phys. 159 045101
[25] Bera I, Payghan P V 2019 Curr. Pharm. Design 25 3339
[26] Arbeitman C R, Rojas P, Ojeda-May P, Garcia M E 2021 Nat. Commun. 12 5407
[27] Semmler M L, Bekeschus S, Schäfer M, Bernhardt T, Fischer T, Witzke K, Seebauer C, Rebl H, Grambow E, Vollmar B, Nebe J B, Metelmann H-R, Woedtke T v, Emmert S, Boeckmann L 2020 Cancers 12 269
[28] Van der Paal J, Neyts E C, Verlackt C C W, Bogaerts A 2016 Chem. Sci. 7 489
[29] Guo F, Zhou J, Wang J, Qian K, Qu H 2023 Phys. Chem. Chem. Phys. 25 14096
[30] Bussi G, Donadio D, Parrinello M 2007 J. Chem. Phys. 126 014101
[31] Parrinello M, Rahman A 1981 J. Appl. Phys. 52 7182
[32] Hoover W G 1985 Phys. Rev. A 31 1695
[33] Nose S 1984 Mol. Phys. 52 255
[34] Hess B, Bekker H, Berendsen H J C, Fraaije J 1997 J. Comput. Chem. 18 1463
[35] Darden T, York D, Pedersen L 1993 J. Chem. Phys. 98 10089
[36] Yusupov M, Van der Paal J, Neyts E C, Bogaerts A 2017 BBA-Gen. Subjects 1861 839
[37] Hu Q, Joshi R P, Schoenbach K H 2005 Phys. Rev. E 72 031902
[38] Hu Q, Viswanadham S, Joshi R P, Schoenbach K H, Beebe S J, Blackmore P F 2005 Phys. Rev. E 71 031914
[39] Schmid N, Eichenberger A P, Choutko A, Riniker S, Winger M, Mark A E, van Gunsteren W F 2011 Eur. Biophy. J. Biophy. 40 843
[40] Cordeiro R M, Yusupov M, Razzokov J, Bogaerts A 2020 J. Phys. Chem. B 124 1082
[41] Neto A J P, Cordeiro R M 2016 BBA-Biomembranes 1858 2191
[42] Razzokov J, Yusupov M, Cordeiro R M, Bogaerts A 2018 J. Phys. D Appl. Phys. 51 365203
[43] Wu S Q, Dong X, Pei X K, Yue Y F, Lu X P 2017Transactions of China Electrotechnical Society 32 82(吴淑群, 董熙, 裴学凯, 岳远富, 卢新培2017 电工技术学报 32 82)
[44] Nakagawa Y, Ono R, Oda T 2011 J. Appl. Phys. 110 073304
[45] Verreycken T, van der Horst R M, Baede A H F M, Van Veldhuizen E M, Bruggeman P J 2012 J. Phys. D Appl. Phys. 45 045205
[46] Vermeylen S, Waele J D, Vanuytsel S, Backer J D, Van de Paal J, Ramakers M, Leyssens K, Marcq E, Van Audenaerde J, Smiths E L J, Dewilde S, Bogaerts A 2016Plasma Processer and Polymers 13 1195
[47] Kim S J, Seong M J, Mun J J, Bae J H, Joh H M, Chung T H 2022Int. J. Mol. Sci. 23 14092
[48] Geboers B, Scheffer H J, Graybill P M, Ruarus A H, Nieuwenhuizen S, Puijk R S, van den Tol P M, Davalos R V, Rubinsky B, de Gruijl T D, Miklavcic D, Meijerink M R 2020 Radiology 295 254
[49] Jiang C L, Davalos R V, Bischof J C 2015 IEEE T. Biomed. Eng. 62 4
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