Abstract：Cold atmospheric plasma,as a new technology to efficiently generate exogenous reactive species, has great potential to become a safe and effective new method for cancer treatment. However, the direct plasma treatment of biological objects has several inherent limitations including shallow penetration depth and short effective time, which makes it difficult to completely release the application potential ofplasmas.Plasma-activated solutions (PAS), an indirect application form of cold atmospheric plasma,have the advantages of relatively long effective time, strong penetration ability, and large action range, which have been widely employed for emerging cancer therapies in recent years. In this paper,recent research advances in the plasma systems for preparing PAS, in vitro anticancer effects and biological mechanisms of PAS, and in vivo anticancer application and biosafety of PAS have been reviewed in detail. Firstly, the preparation and regulation processes of PAS are summarized in terms of plasma discharge types, solutions types and activation methods. For the preparation of PAS in biomedical applications, the types of plasma include dielectric barrier discharge plasma, plasma jet, gliding arc discharge plasma and high-frequency (microwave, radiofrequency) discharge plasma; the types of solutions include deionized water, normal saline, phosphate buffer saline and cell culture medium; the activation methods include direct plasma activation and indirect plasma activation depending on whether plasma is in contact with solutions.The type of plasma discharge devices, the initial environment provided by different solutions and the choice of activation methods all determine the activation efficiency of plasma and affect the composition of reactive species in PAS. Secondly, the in vitro anticancer research status of PAS is reviewed. In the PAS-enabled cancer treatment, cancer cells are generally treated by the plasma-activated cell culture medium or cell culture medium mixed with a volume of PAS. The in vitro anticancer cell models, including cancer cells, drug-resistant cancer cells and 3D tumor spheroids, are compared to fully evaluate the inactivation effect of PAS on cancer cells in different states. Further attempts to understand the PAS anticancer mechanisms are initialized: Cancer cells usually show higher levels of endogenous reactive oxygen species compared with normal cells, and the selective anticancer effects of PAS are achieved by supplying low-dose exogenous reactive species to cancer cells, which makes cancer cells to achieve the lethal threshold faster than normal cells. Finally, the in vivo anticancer research status of PAS is reviewed. At present, the in vivo anticancer ways using PAS mainly include the pericarcinomatous tissue injection and intraluminal perfusion. The former is mainly selected for the treatment of solid tumors located in deep tissues, and intraluminal perfusion is mainly used for the treatment of tumor tissues located in the cavity (such as the peritoneal cavity, bladder, etc.). In addition, the long-term biosafety of PAS in mice has been confirmed, but there are no reports about the biosafety of PAS in clinical applications. The researches of PAS cancer treatment are in the ascendant, and much work remains to be accomplished, including the exploration of insightful anticancer mechanisms, further improvements of anticancer effects, the expansion oftherapeutic scope and the optimization of combined therapies. This paper summarizes recent progresses in the PAS-enabled cancer therapy, and the corresponding theory and methods can provide an important reference for other medical application studies (such as infectious disease treatment).
张浩, 张基珅, 许德晖, 刘定新, 荣命哲. 等离子体活化水溶液用于癌症治疗的研究综述[J]. 电工技术学报, 2023, 38(zk1): 231-246.
Zhang Hao, Zhang Jishen, Xu Dehui, Liu Dingxin, Rong Mingzhe. Advances of Plasma-Activated Solutions for Cancer Therapy. Transactions of China Electrotechnical Society, 2023, 38(zk1): 231-246.
[1] Sung H, Ferlay J, Siegel R L, et al.Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA: A Cancer Journal for Clinicians, 2021, 71(3): 209-249. [2] Chen Wanqing, Zheng Rongshou, Baade P D, et al.Cancer statistics in China, 2015[J]. CA: A Cancer Journal for Clinicians, 2016, 66(2): 115-132. [3] Bruheim K, Guren M G, Skovlund E, et al.Late side effects and quality of life after radiotherapy for rectal cancer[J]. International Journal of Radiation Oncology Biology Physics, 2010, 76(4): 1005-1011. [4] Monsuez J J, Charniot J C, Vignat N, et al.Cardiac side-effects of cancer chemotherapy[J]. International Journal of Cardiology, 2010, 144(1): 3-15. [5] Lu X, Naidis G V, Laroussi M, et al.Guided ionization waves: theory and experiments[J]. Physics Reports, 2014, 540(3): 123-166. [6] Kong M G, Kroesen G, Morfill G, et al.Plasma medicine: an introductory review[J]. New Journal of Physics, 2009, 11(11): 115012. [7] 王瑞雪, 李忠文, 虎攀, 等. 低温等离子体化学毒剂洗消技术研究进展[J]. 电工技术学报, 2021, 36(13): 2767-2781. Wang Ruixue, Li Zhongwen, Hu Pan, et al.Review of research progress of plasma chemical warfare agents degradation[J]. Transactions of China Electrotechnical Society, 2021, 36(13): 2767-2781. [8] 夏文杰, 刘定新. Ar等离子体射流处理乙醇水溶液的放电特性及灭菌效应[J]. 电工技术学报, 2021, 36(4): 765-776. Xia Wenjie, Liu Dingxin.Discharge characteristics and bactericidal effect of Ar plasma jet treating ethanol aqueous solution[J]. Transactions of China Electrotechnical Society, 2021, 36(4): 765-776. [9] Zhang Xianhui, Li Maojin, Zhou Rouli, et al.Ablation of liver cancer cells in vitro by a plasma needle[J]. Applied Physics Letters, 2008, 93(2): 021502. [10] Majumdar A, Ummanni R, Schröder K, et al. Cancer cells (MCF-7, Colo-357,LNCaP) viability on amorphous hydrogenated carbon nitride film deposited by dielectric barrier discharge plasma[J]. Journal of Applied Physics, 2009, 106(3): 034702.1-034702.5. [11] Ma Yonghao, Ha C S, Hwang S W, et al.Non-thermal atmospheric pressure plasma preferentially induces apoptosis in p53-mutated cancer cells by activating ROS stress-response pathways[J]. PLoS One, 2014, 9(4): e91947. [12] Guerrero-Preston R, Ogawa T, Uemura M, et al.Cold atmospheric plasma treatment selectively targets head and neck squamous cell carcinoma cells[J]. International Journal of Molecular Medicine, 2014, 34(4): 941-946. [13] Duan J, Lu X, He G. The selective effect of plasma activated medium in an in vitro co-culture of liver cancer and normal cells[J]. Journal of Applied Physics, 2017, 121(1): 013302.1-013302.6. [14] Ratovitski E A, Cheng Xiaoqian, Yan Dayun, et al.Anti-cancer therapies of 21st century: novel approach to treat human cancers using cold atmospheric plasma[J]. Plasma Processes and Polymers, 2014, 11(12): 1128-1137. [15] Schlegel J, Köritzer J, Boxhammer V.Plasma in cancer treatment[J]. Clinical Plasma Medicine, 2013, 1(2): 2-7. [16] 刘定新, 何桐桐, 张浩. 等离子体对人体组织的渗透作用: 研究现状与前沿问题[J]. 高电压技术, 2019, 45(7): 2329-2342. Liu Dingxin, He Tongtong, Zhang Hao.Penetration effect of gas plasmas on human tissues: state-of-the-art and current issues[J]. High Voltage Engineering, 2019, 45(7): 2329-2342. [17] Chen C, Liu D X, Liu Z C, et al.A model of plasma-biofilm and plasma-tissue interactions at ambient pressure[J]. Plasma Chemistry and Plasma Processing, 2014, 34(3): 403-441. [18] Norberg S A, Tian Wei, Johnsen E, et al.Atmospheric pressure plasma jets interacting with liquid covered tissue: touching and not-touching the liquid[J]. Journal of Physics D: Applied Physics, 2014, 47(47): 475203. [19] Tanaka H, Mizuno M, Ishikawa K, et al.Plasma-activated medium selectively kills glioblastoma brain tumor cells by down-regulating a survival signaling molecule, AKT kinase[J]. Plasma Medicine, 2011, 1(3/4): 265-277. [20] Nakamura K, Peng Yang, Utsumi F, et al.Novel intraperitoneal treatment with non-thermal plasma-activated medium inhibits metastatic potential of ovarian cancer cells[J]. Scientific Reports, 2017, 7(1): 1-14. [21] Mohades S, Laroussi M, Sears J, et al.Evaluation of the effects of a plasma activated medium on cancer cells[J]. Physics of Plasmas, 2015, 22(12): 122001. [22] Adachi T, Tanaka H, Nonomura S, et al.Plasma-activated medium induces A549 cell injury via a spiral apoptotic cascade involving the mitochondrial-nuclear network[J]. Free Radical Biology and Medicine, 2015, 79: 28-44. [23] Utsumi F, Kajiyama H, Nakamura K, et al.Effect of indirect nonequilibrium atmospheric pressure plasma on anti-proliferative activity against chronic chemo-resistant ovarian cancer cells in vitro and in vivo[J]. PLoS One, 2013, 8(12): e81576. [24] Takeda S, Yamada S, Hattori N, et al.Intraperitoneal administration of plasma-activated medium: proposal of a novel treatment option for peritoneal metastasis from gastric cancer[J]. Annals of Surgical Oncology, 2017, 24(5): 1188-1194. [25] Kumar K N, Bhagirath G, Ying L, et al.Biological and medical application of plasma-activated media, water and solutions[J]. Biological Chemistry, 2018, 400(1): 39-62. [26] Keidar M, Yan Dayun, Sherman J H. Indirect CAP treamtent, the application of the cold atmospheric plasma-activated solutions in cancer treatment[M]// Cold Plasma Cancer Therapy: Morgan & Claypool Publishers, 2019: 6-1-6-11. [27] 戴栋, 宁文军, 邵涛. 大气压低温等离子体的研究现状与发展趋势[J]. 电工技术学报, 2017, 32(20): 1-9. Dai Dong, Ning Wenjun, Shao Tao.A review on the state of art and future trends of atmospheric pressure low temperature plasmas[J]. Transactions of China Electrotechnical Society, 2017, 32(20): 1-9. [28] 章程, 邵涛, 龙凯华, 等. 大气压空气中纳秒脉冲介质阻挡放电均匀性的研究[J]. 电工技术学报, 2010, 25(1): 30-36. Zhang Cheng, Shao Tao, Long Kaihua, et al.Uniform of unipolar nanosecond pulse DBD in atmospheric air[J]. Transactions of China Electrotechnical Society, 2010, 25(1): 30-36. [29] Ma Jie, Zhang Hao, Cheng Cheng, et al.Contribution of hydrogen peroxide to non-thermal atmospheric pressure plasma induced A549 lung cancer cell damage[J]. Plasma Processes and Polymers, 2017, 14(7): 1600162. [30] Liu Z C, Liu D X, Chen C, et al.Physicochemical processes in the indirect interaction between surface air plasma and deionized water[J]. Journal of Physics D: Applied Physics, 2015, 48(49): 495201. [31] Metelmann H R.Comprehensive clinical plasma medicine: cold physical plasma for medical application[M]. [32] Morfill G E, Shimizu T, Steffes B, et al.Nosocomial infections—a new approach towards preventive medicine using plasmas[J]. New Journal of Physics, 2009, 11(11): 115019. [33] Liu D X, Liu Z C, Chen C, et al.Aqueous reactive species induced by a surface air discharge: heterogeneous mass transfer and liquid chemistry pathways[J]. Scientific Reports, 2016, 6(1): 1-11. [34] 方志, 刘源, 蔡玲玲. 大气压氩等离子体射流的放电特性[J]. 高电压技术, 2012, 38(7):1613-1622. Fang Zhi, Liu Yuan, Cai Lingling.Discharge characteristics of atmosphere pressure plasma jet in Ar[J]. High Voltage Engineering, 2012, 38(7):1613-1622. [35] 吴淑群, 聂兰兰, 卢新培. 大气压非平衡等离子体射流[J]. 高电压技术, 2015, 41(8): 2602-2624. Wu Shuqun, Nie Lanlan, Lu Xinpei.Atmospheric-pressure non-equilibrium plasma jets[J]. High Voltage Engineering, 2015, 41(8): 2602-2624. [36] 许桂敏, 张冠军, 姚聪伟, 等. 大气压氩气等离子体射流在不同作用状态下的光电特性[J]. 高电压技术, 2019, 45(5): 1375-1386. Xu Guimin, Zhang Guanjun, Yao Congwei, et al.Optical and electrical characteristics of atmospheric pressure argon plasma jet under different interaction states[J]. High Voltage Engineering, 2019, 45(5): 1375-1386. [37] 吴淑群, 董熙, 裴学凯, 等. 基于激光诱导荧光法诊断大气压低温等离子体射流中OH自由基和O原子的时空分布[J]. 电工技术学报, 2017, 32(8): 82-94. Wu Shuqun, Dong Xi, Pei Xuekai, et al.Laser induced fluorescence diagnostics of the temporal and spatial distribution of OH radicals and O atom in a low temperature plasma jet at atmospheric pressure[J]. Transactions of China Electrotechnical Society, 2017, 32(8): 82-94. [38] Shashurin A, Shneider M N, Dogariu A, et al. Temporary-resolved measurement of electron density in small atmospheric plasmas[J]. Applied Physics Letters, 2010, 96(17): ): 171502. [39] Xu Han, Chen Chen, Liu Dingxin, et al.Contrasting characteristics of aqueous reactive species induced by cross-field and linear-field plasma jets[J]. Journal of Physics D: Applied Physics, 2017, 50(24): 245201. [40] Brisset J L, Moussa D, Doubla A, et al.Chemical reactivity of discharges and temporal post-discharges in plasma treatment of aqueous media: examples of gliding discharge treated solutions[J]. Industrial & Engineering Chemistry Research, 2008, 47(16): 5761-5781. [41] 刘程, 张贵新, 王强, 等. 大气压微波等离子体处理有机废气的实验研究[J]. 高电压技术, 2017, 43(8): 2673-2679. Liu Cheng, Zhang Guixin, Wang Qiang, et al.Experimental study of organic waste gas treatment by microwave plasma generated at atmospheric pressure[J]. High Voltage Engineering, 2017, 43(8): 2673-2679. [42] Chen Zeyu, Cui Qingjie, Chen Chen, et al.Inactivation of myeloma cancer cells by helium and argon plasma jets: the effect comparison and the key reactive species[J]. Physics of Plasmas, 2018, 25(2): 023508. [43] Chen Zeyu, Liu Dingxin, Chen Chen, et al.Analysis of the production mechanism of H2O2 in water treated by helium DC plasma jets[J]. Journal of Physics D: Applied Physics, 2018, 51(32): 325201. [44] Olszewski P, Li J F, Liu D X, et al.Optimizing the electrical excitation of an atmospheric pressure plasma advanced oxidation process[J]. Journal of Hazardous Materials, 2014, 279: 60-66. [45] Chen Zhitong, Lin Li, Cheng Xiaoqian, et al.Effects of cold atmospheric plasma generated in deionized water in cell cancer therapy[J]. Plasma Processes and Polymers, 2016, 13(12): 1151-1156. [46] Yu Xiaoying.Critical evaluation of rate constants and equilibrium constants of hydrogen peroxide photolysis in acidic aqueous solutions containing chloride ions[J]. Journal of Physical and Chemical Reference Data, 2004, 33: 747-763. [47] Yu Xiaoying, Barker J R.Hydrogen peroxide photolysis in acidic aqueous solutions containing chloride ions. I. chemical mechanism[J]. The Journal of Physical Chemistry A, 2003, 107(9): 1313-1324. [48] Liu Zhi chao, Guo Li, Liu Ding xin, et al. Chemical kinetics and reactive species in normal saline activated by a surface air discharge[J]. Plasma Processes and Polymers, 2017, 14(4/5): 1600113. [49] Jirásek V, Lukeš P.Formation of reactive chlorine species in saline solution treated by non-equilibrium atmospheric pressure He/O2 plasma jet[J]. Plasma Sources Science and Technology, 2019, 28(3): 035015. [50] Candeias L P, Patel K B, Stratford M R L, et al. Free hydroxyl radicals are formed on reaction between the neutrophil-derived species Superoxide anion and hypochlorous acid[J]. FEBS Letters, 1993, 333(1/2): 151-153. [51] Chen Zhitong, Lin Li, Gjika E, et al.Selective treatment of pancreatic cancer cells by plasma-activated saline solutions[J]. IEEE Transactions on Radiation and Plasma Medical Sciences, 2018, 2(2): 116-120. [52] Freund E, Liedtke K R, van der Linde J, et al. Physical plasma-treated saline promotes an immunogenic phenotype in CT26 colon cancer cells in vitro and in vivo[J]. Scientific Reports, 2019, 9: 634. [53] Akkoc A, Celik H, Arslan N, et al.The effects of different environmental pH on healing of tympanic membrane: an experimental study[J]. European Archives of Oto-Rhino-Laryngology, 2016, 273(9): 2503-2508. [54] Buxton G, Greenstock C, Helman W, et al.Critical Review of rate constants for reactions of hydrated electrons, hydrogen atoms and hydroxyl radicals (⋅OH/⋅O- in Aqueous Solution[J]. Journal of Physical and Chemical Reference Data, 1988, 17: 513-886. [55] Van Boxem W, Van der Paal J, Gorbanev Y, et al. Anti-cancer capacity of plasma-treated PBS: effect of chemical composition on cancer cell cytotoxicity[J]. Scientific Reports, 2017, 7(1): 1-15. [56] Boehm D, Heslin C, Cullen P J, et al.Cytotoxic and mutagenic potential of solutions exposed to cold atmospheric plasma[J]. Scientific Reports, 2016, 6(1): 1-14. [57] Yan Dayun, Talbot A, Nourmohammadi N, et al.Principles of using cold atmospheric plasma stimulated media for cancer treatment[J]. Scientific Reports, 2015, 5(1): 1-17. [58] Kurake N, Tanaka H, Ishikawa K, et al.Cell survival of glioblastoma grown in medium containing hydrogen peroxide and/or nitrite, or in plasma-activated medium[J]. Archives of Biochemistry and Biophysics, 2016, 605: 102-108. [59] Anderson C E, Cha N R, Lindsay A D, et al.The role of interfacial reactions in determining plasma-liquid chemistry[J]. Plasma Chemistry and Plasma Processing, 2016, 36(6): 1393-1415. [60] 孔刚玉, 刘定新. 气体等离子体与水溶液的相互作用研究: 意义、挑战与新进展[J]. 高电压技术, 2014, 40(10): 2956-2965. Kong Gangyu, Liu Dingxin.Researches on the interaction between gas plasmas and aqueous solutions: significance, challenges and new progresses[J]. High Voltage Engineering, 2014, 40(10): 2956-2965. [61] Wang Zifeng, Xu Shengduo, Liu Dingxin, et al.An integrated device for preparation of plasma-activated media with bactericidal properties: an in vitro and in vivo study[J]. Contributions to Plasma Physics, 2022, 62(3): e202100125. [62] Torii K, Yamada S, Nakamura K, et al.Effectiveness of plasma treatment on gastric cancer cells[J]. Gastric Cancer, 2015, 18(3): 635-643. [63] Yan Dayun, Cui Haitao, Zhu Wei, et al.The specific vulnerabilities of cancer cells to the cold atmospheric plasma-stimulated solutions[J]. Scientific Reports, 2017, 7(1): 1-12. [64] Steeg P S.Targeting metastasis[J]. Nature Reviews Cancer, 2016, 16(4): 201-218. [65] Yamada K M, Cukierman E.Modeling tissue morphogenesis and cancer in 3D[J]. Cell, 2007, 130(4): 601-610. [66] Abbott A.Biology’s new dimension[J]. Nature, 2003, 424(6951): 870-872. [67] Lee J, Cuddihy M J, Kotov N A.Three-dimensional cell culture matrices: state of the art[J]. Tissue Engineering Part B: Reviews, 2008, 14(1): 61-86. [68] Lee J, Lilly G D, Doty R C, et al. In vitro toxicity testing of nanoparticles in 3D cell culture[J]. Small, 2009: NA. [69] Sowa M B, Chrisler W B, Zens K D, et al.Three-dimensional culture conditions lead to decreased radiation induced cytotoxicity in human mammary epithelial cells[J]. Fundamental and Molecular Mechanisms of Mutagenesis, 2010, 687(1/2): 78-83. [70] Edmondson R, Broglie J J, Adcock A F, et al.Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors[J]. Assay and Drug Development Technologies, 2014, 12(4): 207-218. [71] Smalley K S M, Lioni M, Herlyn M. Life ins't flat: taking cancer biology to the next dimension[J]. In Vitro Cellular & Developmental Biology - Animal, 2006, 42(8): 242-247. [72] Judée F, Fongia C, Ducommun B, et al.Short and long time effects of low temperature Plasma Activated Media on 3D multicellular tumor spheroids[J]. Scientific Reports, 2016, 6(1): 1-12. [73] Griseti E, Kolosnjaj-Tabi J, Gibot L, et al.Pulsed electric field treatment enhances the cytotoxicity of plasma-activated liquids in a three-dimensional human colorectal cancer cell model[J]. Scientific Reports, 2019, 9: 7583. [74] Chauvin J, Judée F, Merbahi N, et al.Effects of plasma activated medium on head and neck FaDu cancerous cells: comparison of 3D and 2D Response[J]. Anti-cancer Agents in Medicinal Chemistry, 2017, 18(6): 776-783. [75] Zhang Jishen, Liu Dingxin, Zhang Hao, et al.Influence of liquid coverage on the anticancer effects of a helium plasma jet on 3D tumor spheroids[J]. Plasma Processes and Polymers, 2020, 17(7): 1900213. [76] Szili E J, Al-Bataineh S A, Bryant P M, et al. Controlling the spatial distribution of polymer surface treatment using atmospheric-pressure microplasma jets[J]. Plasma Processes and Polymers, 2011, 8(1): 38-50. [77] Desmet G, Michelmore A, Szili E J, et al.On the effects of atmospheric-pressure microplasma array treatment on polymer and biological materials[J]. RSC Advances, 2013, 3(32): 13437-13445. [78] Zhang Hao, Zhang Jishen, Liu Zhijie, et al.Evaluation of the anticancer effects induced by cold atmospheric plasma in 2D and 3D cell-culture models[J]. Plasma Processes and Polymers, 2019, 16(12): 1900072. [79] Zhang Hao, Zhang Jishen, Xu Shengduo, et al.Antitumor effects of hyperthermia with plasma-treated solutions on 3D bladder tumor spheroids[J]. Plasma Processes and Polymers, 2021, 18(10): 2100070. [80] Trachootham D, Alexandre J, Huang Peng.Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach?[J]. Nature Reviews Drug Discovery, 2009, 8(7): 579-591. [81] Wang Jie, Yi Jing.Cancer cell killing via ROS: to increase or decrease, that is the question[J]. Cancer Biology & Therapy, 2008, 7(12): 1875-1884. [82] Cairns R A, Harris I S, Mak T W.Regulation of cancer cell metabolism[J]. Nature Reviews Cancer, 2011, 11(2): 85-95. [83] Wu Defeng, Cederbaum A I.Alcohol, oxidative stress, and free radical damage[J]. Alcohol Research & Health: the Journal of the National Institute on Alcohol Abuse and Alcoholism, 2003, 27(4): 277-284. [84] Graves D B.The emerging role of reactive oxygen and nitrogen species in redox biology and some implications for plasma applications to medicine and biology[J]. Journal of Physics D: Applied Physics, 2012, 45(26): 263001. [85] Kalghatgi S, Kelly C M, Cerchar E, et al.Effects of non-thermal plasma on mammalian cells[J]. PLoS One, 2011, 6(1): e16270. [86] 许德晖, 崔庆杰, 许宇静, 等. 等离子体医学及其在肿瘤治疗中的应用[J]. 生物化学与生物物理进展, 2017, 44(4): 279-292. Xu Dehui, Cui Qingjie, Xu Yujing, et al.Plasma medicine and the application in tumor therapy[J]. China Industrial Economics, 2017, 44(4): 279-292. [87] Zhang Hao, Zhang Jishen, Guo Bo, et al.The antitumor effects of plasma-activated saline on muscle-invasive bladder cancer cells in vitro and in vivo demonstrate its feasibility as a potential therapeutic approach[J]. Cancers, 2021, 13(5): 1042. [88] Zhao Shasha, Xiong Zilan, Mao Xiang, et al.Atmospheric pressure room temperature plasma jets facilitate oxidative and nitrative stress and lead to endoplasmic reticulum stress dependent apoptosis in HepG2 cells[J]. PLoS One, 2013, 8(8): e73665. [89] Van der Paal J, Neyts E C, Verlackt C C W, et al. Effect of lipid peroxidation on membrane permeability of cancer and normal cells subjected to oxidative stress[J]. Chemical Science, 2016, 7(1): 489-498. [90] Ishaq M, Kumar S, Varinli H, et al.Atmospheric gas plasma-induced ROS production activates TNF-ASK1 pathway for the induction of melanoma cancer cell apoptosis[J]. Molecular Biology of the Cell, 2014, 25(9): 1523-1531. [91] Nie L, Duan J, Lu X.On the penetration depth of reactive oxygen and nitrogen species generated by a plasma jet through real biological tissue[J]. Clinical Plasma Medicine, 2018, 9: 32. [92] Duan J, Gan L, Nie L, et al.On the penetration of reactive oxygen and nitrogen species generated by a plasma jet into and through mice skin with/without stratum corneum[J]. Physics of Plasmas, 2019, 26(4): 043504. [93] Liu Jinren, Wu Yueming, Xu Guimin, et al.Low-temperature plasma induced melanoma apoptosis by triggering a p53/PIGs/caspase-dependent pathway in vivo and in vitro[J]. Journal of Physics D: Applied Physics, 2019, 52(31): 315204. [94] Saadati F, Mahdikia H, Abbaszadeh H A, et al.Comparison of direct and indirect cold atmospheric-pressure plasma methods in the B16F10 melanoma cancer cells treatment[J]. Scientific Reports, 2018, 8(1): 1-15. [95] Liedtke K R, Bekeschus S, Kaeding A, et al.Non-thermal plasma-treated solution demonstrates antitumor activity against pancreatic cancer cells in vitro and in vivo[J]. Scientific Reports, 2017, 7(1): 1-12. [96] Qi Miao, Xu Dehui, Wang Shuai, et al.In vivo metabolic analysis of the anticancer effects of plasma-activated saline in three tumor animal models[J]. Biomedicines, 2022, 10(3): 528. [97] Xu Dehui, Cui Qingjie, Xu Yujing, et al.Systemic study on the safety of immuno-deficient nude mice treated by atmospheric plasma-activated water[J]. Plasma Science and Technology, 2018, 20(4): 044003. [98] Nastasa V, Pasca A S, Malancus R N, et al.Toxicity assessment of long-term exposure to non-thermal plasma activated water in mice[J]. International Journal of Molecular Sciences, 2021, 22(21): 11534.
2023, Vol. 38 
