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2000
Volume 32, Issue 4
  • ISSN: 1381-6128
  • E-ISSN: 1873-4286

Abstract

Introduction

In recent decades, Cold Atmospheric Plasma (CAP) has become increasingly popular in healthcare for managing diseases, especially skin cancer. This study aimed to assess the preclinical safety of an indigenously developed dielectric barrier discharge-CAP (DBD) device and its cytotoxic efficacy against melanoma cells while adhering to OECD 402 guidelines for acute dermal toxicity study. The safety evaluation includes studies on mouse peritoneal exudates and acute dermal toxicity tests on Wistar rats.

Methods

The study of mice peritoneal cells treated for up to 120 seconds, showed a survival rate of over 90% up to 90 seconds of CAP treatment for applied voltage 18.6 kV at 20 kHz with no significant difference with control. In the acute dermal toxicity tests, CAP exposure for up to 30 seconds caused minimal inflammatory cell infiltration and no significant Dermal Inflammation Scoring (DIS) (<1).

Results

The efficacy study against G361 human melanoma cells showed reduced cell viability by ~50% (MTT assay) upon 30 seconds of CAP treatment for applied voltage 24 kV at 20 kHz through ROS-mediated apoptosis, confirmed by a 3-fold increase in intracellular reactive oxygen species levels and nuclear fragmentation (4',6-diamidino-2-phenylindole staining). Annexin V/PI (propium iodide) staining further revealed ~30% apoptosis after 24 hours of incubation. These findings establish the developed DBD-CAP device is safe for rat skin exposure durations of up to 30 seconds and effective in inducing apoptosis in melanoma cells.

Conclusion

This study supports CAP's optimization for clinical applications and its integration with existing therapies for enhanced outcomes. However, further study is needed to examine the possible risks associated with using CAP devices in the biomedical field.

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2026-01-31

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References

  1. SiegelR.L. GiaquintoA.N. JemalA. Cancer statistics, 2024.CA Cancer J. Clin.2024741124910.3322/caac.21820 38230766
     [Google Scholar]
  2. PashazadehA. BoeseA. FriebeM. Radiation therapy techniques in the treatment of skin cancer: an overview of the current status and outlook.J. Dermatolog. Treat.201930883183910.1080/09546634.2019.1573310 30703334
     [Google Scholar]
  3. NasimM. KhanM. ParveenR. GullA. KhanS. AliJ. Novel paradigm of therapeutic intervention for skin cancer: challenges and opportunities.Future Journal of Pharmaceutical Sciences202410111210.1186/s43094‑024‑00686‑2
     [Google Scholar]
  4. QuaziS.J. AslamN. SaleemH. RahmanJ. KhanS. The surgical margin of excision in basal cell carcinoma: a systematic review of literature.Cureus2020127e921110.7759/cureus.9211 32821563
     [Google Scholar]
  5. KuflikE.G. Cryosurgery for skin cancer: 30-year experience and cure rates.Dermatol. Surg.2004302 Pt 229730010.1097/00042728‑200402002‑00011 14871224
     [Google Scholar]
  6. YanovskyR.L. BartensteinD.W. RogersG.S. IsakoffS.J. ChenS.T. Photodynamic therapy for solid tumors: A review of the literature.Photodermatol. Photoimmunol. Photomed.201935529530310.1111/phpp.12489 31155747
     [Google Scholar]
  7. PaulsonK.G. LahmanM.C. ChapuisA.G. BrownellI. Immunotherapy for skin cancer.Int. Immunol.201931746547510.1093/intimm/dxz012 30753483
     [Google Scholar]
  8. SinghV. SheikhA. AbourehabM. KesharwaniP. Dostarlimab as a miracle drug: rising hope against cancer treatment.Biosensors202212861710.3390/bios12080617 36005013
     [Google Scholar]
  9. LukeJ.J. SchwartzG.K. Chemotherapy in the management of advanced cutaneous malignant melanoma.Clin. Dermatol.201331329029710.1016/j.clindermatol.2012.08.016 23608448
     [Google Scholar]
  10. NurgaliK. JagoeR.T. AbaloR. Adverse effects of cancer chemotherapy: Anything new to improve tolerance and reduce sequelae?Front. Pharmacol.2018924510.3389/fphar.2018.00245 29623040
     [Google Scholar]
  11. RohaanM.W. BorchT.H. van den BergJ.H. Tumor-infiltrating lymphocyte therapy or ipilimumab in advanced melanoma.N. Engl. J. Med.2022387232113212510.1056/NEJMoa2210233 36477031
     [Google Scholar]
  12. LiuC. ZhaJ. SunT. Cold atmospheric plasma attenuates skin cancer via ROS induced apoptosis.Mol. Biol. Rep.202451151810.1007/s11033‑024‑09486‑6 38622261
     [Google Scholar]
  13. Aghebati-MalekiA. DolatiS. AhmadiM. Nanoparticles and cancer therapy: Perspectives for application of nanoparticles in the treatment of cancers.J. Cell. Physiol.202023531962197210.1002/jcp.29126 31441032
     [Google Scholar]
  14. KaushikN.K. KaushikN. YooK.C. Low doses of PEG-coated gold nanoparticles sensitize solid tumors to cold plasma by blocking the PI3K/AKT-driven signaling axis to suppress cellular transformation by inhibiting growth and EMT.Biomaterials20168711813010.1016/j.biomaterials.2016.02.014 26921841
     [Google Scholar]
  15. BustinS.A. JellingerK.A. Advances in molecular medicine: unravelling disease complexity and pioneering precision healthcare.Int. J. Mol. Sci.202324181416810.3390/ijms241814168 37762471
     [Google Scholar]
  16. BranýD. DvorskáD. HalašováE. ŠkovierováH. Cold atmospheric plasma: A powerful tool for modern medicine.Int. J. Mol. Sci.2020218293210.3390/ijms21082932 32331263
     [Google Scholar]
  17. HoffmannC. BerganzaC. ZhangJ. Cold Atmospheric Plasma: methods of production and application in dentistry and oncology.Med. Gas Res.2013312110.1186/2045‑9912‑3‑21 24083477
     [Google Scholar]
  18. von WoedtkeT. EmmertS. MetelmannH.R. RupfS. WeltmannK.D. Perspectives on cold atmospheric plasma (CAP) applications in medicine.Phys. Plasmas202027707060110.1063/5.0008093
     [Google Scholar]
  19. XuD. LuoX. XuY. The effects of cold atmospheric plasma on cell adhesion, differentiation, migration, apoptosis and drug sensitivity of multiple myeloma.Biochem. Biophys. Res. Commun.201647341125113210.1016/j.bbrc.2016.04.027 27067049
     [Google Scholar]
  20. SunT. ZhangX. HouC. Cold plasma irradiation attenuates atopic dermatitis via enhancing HIF-1α-induced MANF transcription expression.Front. Immunol.20221394121910.3389/fimmu.2022.941219 35911675
     [Google Scholar]
  21. DubeyS.K. ParabS. AlexanderA. Cold atmospheric plasma therapy in wound healing.Process Biochem.202211211212310.1016/j.procbio.2021.11.017
     [Google Scholar]
  22. ZhaiS. KongM.G. XiaY. Cold atmospheric plasma ameliorates skin diseases involving reactive oxygen/nitrogen species-mediated functions.Front. Immunol.20221386838610.3389/fimmu.2022.868386 35720416
     [Google Scholar]
  23. LimanowskiR. YanD. LiL. KeidarM. Preclinical cold atmospheric plasma cancer treatment.Cancers20221414346110.3390/cancers14143461 35884523
     [Google Scholar]
  24. LaroussiM. Cold plasma in medicine and healthcare: The new frontier in low temperature plasma applications.Front. Phys. (Lausanne)202087410.3389/fphy.2020.00074
     [Google Scholar]
  25. AlqutaibiA.Y. AljohaniA. AlduriA. The effectiveness of Cold Atmospheric Plasma (CAP) on bacterial reduction in dental implants: A systematic review.Biomolecules20231310152810.3390/biom13101528 37892210
     [Google Scholar]
  26. KimN. LeeS. LeeS. Portable Cold Atmospheric Plasma Patch‐Mediated Skin Anti‐Inflammatory Therapy.Adv. Sci. (Weinh.)2022934220280010.1002/advs.202202800 36180414
     [Google Scholar]
  27. ZuborP. WangY. LiskovaA. Cold atmospheric pressure plasma (CAP) as a new tool for the management of vulva cancer and vulvar premalignant lesions in gynaecological oncology.Int. J. Mol. Sci.20202121798810.3390/ijms21217988 33121141
     [Google Scholar]
  28. Chandra SharmaM. SharmaM. Novel applications of Cold Atmospheric Plasma for the treatment of Plaque Psoriasis.Research Journal of Pharmacy and Technology20231652543254810.52711/0974‑360X.2023.00418
     [Google Scholar]
  29. HeinlinJ. IsbaryG. StolzW. A randomized two‐sided placebo‐controlled study on the efficacy and safety of atmospheric non‐thermal argon plasma for pruritus.J. Eur. Acad. Dermatol. Venereol.201327332433110.1111/j.1468‑3083.2011.04395.x 22188329
     [Google Scholar]
  30. BaiF. RanY. ZhaiS. XiaY. Cold Atmospheric Plasma: A Promising and Safe Therapeutic Strategy for Atopic Dermatitis.Int. Arch. Allergy Immunol.2023184121184119710.1159/000531967 37703833
     [Google Scholar]
  31. MitraS. NguyenL.N. AkterM. ParkG. ChoiE.H. KaushikN.K. Impact of ROS generated by chemical, physical, and plasma techniques on cancer attenuation.Cancers2019117103010.3390/cancers11071030 31336648
     [Google Scholar]
  32. ShakouriR. KhaniM.R. SamsavarS. In vivo study of the effects of a portable cold plasma device and vitamin C for skin rejuvenation.Sci. Rep.20211112191510.1038/s41598‑021‑01341‑z 34753995
     [Google Scholar]
  33. MaitraS. BhattacharyaD. PaulS. Programmed cell death protein 1 (PD-1) in relation to PANoptosis: Immune pharmacological targets for management of breast adenocarcinoma.Endocr. Metab. Immune Disord. Drug Targets2023231315711585
     [Google Scholar]
  34. ShenS. ShaoY. LiC. Different types of cell death and their shift in shaping disease.Cell Death Discov.20239128410.1038/s41420‑023‑01581‑0 37542066
     [Google Scholar]
  35. AltayyarS.S. 2020; The essential principles of safety and effectiveness for medical devices and the role of standards.Med. Devices202013495510.2147/MDER.S235467
     [Google Scholar]
  36. Antich-IsernP. Caro-BarriJ. Aparicio-BlancoJ. The combination of medical devices and medicinal products revisited from the new European legal framework.Int. J. Pharm.202160712099210.1016/j.ijpharm.2021.120992 34390808
     [Google Scholar]
  37. BiswasS. Borpatra GohainR. TalukdarP. ThakurD. High voltage high frequency pulse power supply for dielectric barrier discharge device to generate cold atmospheric plasma.Indian Patent, 2023110628592023
  38. TalukdarP. GohainR.B. BharadwajP. ThakurD. BiswasS. Inactivation of Candida albicans, Staphylococcus aureus and multidrug-resistant Escherichia coli with dielectric barrier discharged cold atmospheric plasma: A comparative study with antimicrobial drugs.J. Med. Microbiol.2025741001965
     [Google Scholar]
  39. GohainR.B. BiswasS. Impact of applied voltage, air gap, and ground arrangement on discharge power and dielectric capacitance in a volume DBD plasma.Physica Scripta20251002025604
     [Google Scholar]
  40. FridmanG. PeddinghausM. BalasubramanianM. Blood coagulation and living tissue sterilization by floating-electrode dielectric barrier discharge in air.Plasma Chem. Plasma Process.200626442544210.1007/s11090‑006‑9024‑4
     [Google Scholar]
  41. BalaA. HaldarP.K. KarB. NaskarS. MazumderU.K. Carbon tetrachloride: A hepatotoxin causes oxidative stress in murine peritoneal macrophage and peripheral blood lymphocyte cells.Immunopharmacol. Immunotoxicol.201234115716210.3109/08923973.2011.590498 21721906
     [Google Scholar]
  42. ZhangX GoncalvesR MosserDM The isolation and characterization of murine macrophages.Curr Protoc Immunol20088311.1, 1410.1002/0471142735.im1401s83 19016445
     [Google Scholar]
  43. StroberW. Trypan blue exclusion test of cell viability.Curr Protoc Immunol ; Appendix 3(Appendix 3B)201510.1002/0471142735.ima03bs111
     [Google Scholar]
  44. TestNo. OECD Guidelines for the Testing of Chemicals, Section 42017Available from: https://www.oecd-ilibrary.org/
  45. KunduS. BalaA. GhoshP. Attenuation of oxidative stress by Allylpyrocatechol in synovial cellular infiltrate of patients with Rheumatoid Arthritis.Free Radic. Res.201145551852610.3109/10715762.2011.555480 21284489
     [Google Scholar]
  46. BhorU. PandeS. Scoring systems in dermatology.Indian J. Dermatol. Venereol. Leprol.200672431532110.4103/0378‑6323.26722 16880586
     [Google Scholar]
  47. AgbajeM. RutlandC.S. MaboniG. Novel inflammatory cell infiltration scoring system to investigate healthy and footrot affected ovine interdigital skin.PeerJ20186e509710.7717/peerj.5097 30002960
     [Google Scholar]
  48. BalaA. MukherjeeP.K. BragaF.C. MatsabisaM.G. Comparative inhibition of MCF-7 breast cancer cell growth, invasion and angiogenesis by Cannabis sativa L. sourced from sixteen different geographic locations.S. Afr. J. Bot.201811915416210.1016/j.sajb.2018.07.022
     [Google Scholar]
  49. XuD. WangB. XuY. Intracellular ROS mediates gas plasma-facilitated cellular transfection in 2D and 3D cultures.Sci. Rep.2016612787210.1038/srep27872 27296089
     [Google Scholar]
  50. WallbergF TenevT MeierP 2016Analysis of apoptosis and necroptosis by fluorescence-activated cell sorting.Cold Spring Harb Protoc 2016; 2016(4): pdb.prot087387.10.1101/pdb.prot087387
     [Google Scholar]
  51. YadavD.K. AdhikariM. KumarS. Cold atmospheric plasma generated reactive species aided inhibitory effects on human melanoma cells: An in vitro and in silico study.Sci. Rep.2020101339610.1038/s41598‑020‑60356‑0 32099012
     [Google Scholar]
  52. SimoncelliE. SchulpenJ. BarlettaF. UV–VIS optical spectroscopy investigation on the kinetics of long-lived RONS produced by a surface DBD plasma source.Plasma Sources Sci. Technol.201928909501510.1088/1361‑6595/ab3c36
     [Google Scholar]
  53. BruggemanP.J. SadeghiN. SchramD.C. LinssV. Gas temperature determination from rotational lines in non-equilibrium plasmas: A review.Plasma Sources Sci. Technol.201423202300110.1088/0963‑0252/23/2/023001
     [Google Scholar]
  54. CassadoA.A. D’Império LimaM.R. BortoluciK.R. Revisiting mouse peritoneal macrophages: Heterogeneity, development, and function.Front. Immunol.2015622510.3389/fimmu.2015.00225 26042120
     [Google Scholar]
  55. LiM. GaoJ. WangL. Basic research and clinical exploration of cold atmospheric plasma for skin wounds.Bioeng. Transl. Med.202385e1055010.1002/btm2.10550 37693064
     [Google Scholar]
  56. AdhikariM. AdhikariB. AdhikariA. Cold atmospheric plasma as a novel therapeutic tool for the treatment of brain cancer.Curr. Pharm. Des.202026192195220610.2174/1381612826666200302105715 32116185
     [Google Scholar]
  57. DomonkosM. TicháP. TrejbalJ. DemoP. Applications of cold atmospheric pressure plasma technology in medicine, agriculture and food industry.Appl. Sci.20211111480910.3390/app11114809
     [Google Scholar]
  58. ZilleA. Plasma technology in fashion and textiles.In: Sustainable technologies for fashion and textiles.Woodhead Publishing202011714210.1016/B978‑0‑08‑102867‑4.00006‑2
     [Google Scholar]
  59. LinS.P. KhumsupanD. ChouY.J. Applications of atmospheric cold plasma in agricultural, medical, and bioprocessing industries.Appl. Microbiol. Biotechnol.2022106237737775010.1007/s00253‑022‑12252‑y 36329134
     [Google Scholar]
  60. Hernández-TorresC.J. Reyes-AcostaY.K. Chávez-GonzálezM.L. Recent trends and technological development in plasma as an emerging and promising technology for food biosystems.Saudi J. Biol. Sci.20222941957198010.1016/j.sjbs.2021.12.023 35531194
     [Google Scholar]
  61. Medical devices must be carefully validated.Nat. Biomed. Eng.20182962562610.1038/s41551‑018‑0302‑2 31015685
     [Google Scholar]
  62. Cold Physical Plasma for Medical Application.GermanySpringer International Publishing2018
     [Google Scholar]
  63. Gay-MimbreraJ. GarcíaM.C. Isla-TejeraB. Rodero-SerranoA. García-NietoA.V. RuanoJ. Clinical and biological principles of cold atmospheric plasma application in skin cancer.Adv. Ther.201633689490910.1007/s12325‑016‑0338‑1 27142848
     [Google Scholar]
  64. EggersB. WagenheimA.M. JungS. Effect of cold atmospheric plasma (CAP) on osteogenic differentiation potential of human osteoblasts.Int. J. Mol. Sci.2022235250310.3390/ijms23052503 35269642
     [Google Scholar]
  65. SilvaN. MarquesJ. Brito da CruzM. LuísH. MataA. SérioS. Cold atmospheric plasma activation of human gingival fibroblasts for improved wound healing.J. Phys. D Appl. Phys.202558202520710.1088/1361‑6463/ad83de
     [Google Scholar]
  66. SharifH. AghayanS. The effect of cold plasma and low-level laser therapy on oral fibroblast proliferation.Immunol Genet J202462677810.18502/igj.v6i2.16411
     [Google Scholar]
  67. FridmanG ShereshevskyA PeddinghausM GutsolA VasiletsV BrooksA Bio-medical applications of non-thermal atmospheric pressure plasma.10.2514/6.2006‑2902
     [Google Scholar]
  68. FridmanG. FriedmanG. GutsolA. ShekhterA.B. VasiletsV.N. FridmanA. Applied plasma medicine.Plasma Process. Polym.20085650353310.1002/ppap.200700154
     [Google Scholar]
  69. D’OrazioJ. JarrettS. Amaro-OrtizA. ScottT. UV radiation and the skin.Int. J. Mol. Sci.2013146122221224810.3390/ijms140612222 23749111
     [Google Scholar]
  70. LeiterU. KeimU. GarbeC. Epidemiology of Skin Cancer: Update 2019.Adv. Exp. Med. Biol.20201268123139
     [Google Scholar]
  71. FabbrociniG. TriassiM. MaurielloM.C. Epidemiology of skin cancer: Role of some environmental factors.Cancers2010241980198910.3390/cancers2041980 24281212
     [Google Scholar]
  72. LabaniS. AsthanaS. RathoreK. SardanaK. Incidence of melanoma and nonmelanoma skin cancers in Indian and the global regions.J. Cancer Res. Ther.202117490691110.4103/jcrt.JCRT_785_19 34528540
     [Google Scholar]
  73. ZhaoB. HeY.Y. Recent advances in the prevention and treatment of skin cancer using photodynamic therapy.Expert Rev. Anticancer Ther.201010111797180910.1586/era.10.154 21080805
     [Google Scholar]
  74. VarshneyK. MazumderR. RaniA. MishraR. KhuranaN. Recent research trends against skin carcinoma - An overview.Curr. Pharm. Des.202430342685270010.2174/0113816128307653240710044902 39051578
     [Google Scholar]
  75. YazdaniZ. PasandiM.S. GolpourM. EslamiM. RafieiA. Effect of cold atmospheric plasma on changing of biomolecular structures involved in apoptosis pathways of melanoma cancer.Skin Res. Technol.2024301e1354410.1111/srt.13544 38174746
     [Google Scholar]
  76. SagwalS.K. BekeschusS. ROS pleiotropy in melanoma and local therapy with physical modalities.Oxid. Med. Cell. Longev.202120211681621410.1155/2021/6816214 34777692
     [Google Scholar]
  77. ArndtS. WackerE. LiY.F. Cold atmospheric plasma, a new strategy to induce senescence in melanoma cells.Exp. Dermatol.201322428428910.1111/exd.12127 23528215
     [Google Scholar]
/content/journals/cpd/10.2174/0113816128335012250122221541
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Pre-clinical Safety Study of Cold Atmospheric Plasma (CAP) Produced by an Inbuilt CAP Device and ROS Mediated Apoptotic Activity in Human Skin Melanoma Cells
Curr. Pharm. Des. 32, 306 (2026); https://doi.org/10.2174/0113816128335012250122221541
/content/journals/cpd/10.2174/0113816128335012250122221541
/content/journals/cpd/10.2174/0113816128335012250122221541
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  • Article Type:     Research Article
Keyword(s): acute dermal toxicity test; Cold atmospheric plasma; cytotoxicity; dermal inflammation scoring; OECD 402 guideline; skin melanoma cells

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