Medical Radiology and Radiation Safety. 2024. Vol. 69. № 4
DOI:10.33266/1024-6177-2024-69-4-13-19
D.T. Petrosova1, D.V. Uskalova1, O.V. Kuzmicheva1, V.O. Saburov3,
E.I. Sarapultseva1, 2
Enhancement of the Cytotoxic Effect of Proton Irradiation by Gold Nanoparticles
1 Obninsk Institute for Nuclear Power Engineering, Obninsk, Russia
2 National Research Nuclear University “MEPhI”, Moscow, Russia
3 A.F. Tsyb Medical Radiological Research Center, Obninsk, Russia
Contact person: D.T. Petrosova, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.
ABSTRACT
Purpose: To evaluate the bioefficiency and biosafety of proton irradiation in combination with gold nanoparticles (AuNPs) on a model of a higher invertebrate animal Daphnia magna from the suborder crustaceans in in vivo experiments.
Materials and methods: The synthesis of AuNPs was carried out by a single-stage method of femtosecond laser ablation. A laboratory culture of Daphnia magna (D. magna) was used. Animals were cultured in a climatostat (model P2). Biological parameters (viability, fertility and cytotoxicity) were evaluated in two consecutive generations (F0) and (F1). Only animals of the parental generation (F0) were exposed to acute irradiation with a scanning proton beam (energy 150 MeV) on the Prometheus proton complex. Viability and fertility D. magna were evaluated in a 21-day experiment on a daily basis. A total of 10 to 60 individuals were analyzed in control and experimental groups. Cytotoxicity was analyzed by an MTT test modified for studies of the effect on invertebrates in in vivo experiments. From 11 to 97 samples were analyzed for cytotoxicity. There were 20 animals in each sample. The results are analyzed by methods of mathematical statistics adjusted for multiple comparisons.
Results: Irradiation at doses of 10 and 30 Gy caused a decrease in animal viability, which was increased in 1.35 times. Reproductive dysfunction was found in both irradiated and first-generation animals. The use of AuNPs did not cause oxidative stress in D. magna, but increased the cytotoxic effect of proton irradiation. AuNPs contributed to the cytotoxic effect.
Conclusions: Since the results obtained are consistent with the data published in the cited articles on vertebrates, it is possible to assume a universal mechanism of cytotoxic effect of proton irradiation in combination with AuNPs on both invertebrates and vertebrates, including humans, and the possibility of using AuNPs as radiosensitizers to enhance the effect of irradiation in binary proton therapy technologies.
Keywords: Daphnia magna, protons, gold nanoparticles (AuNPs), viability, fertility, cytotoxicity, transgeneration effect
For citation: Petrosova DT, Uskalova DV, Kuzmicheva OV, Saburov VO., Sarapultseva E.I. Enhancement of the Cytotoxic Effect of Proton Irradiation by Gold Nanoparticles. Medical Radiology and Radiation Safety. 2024;69(4):13–19. (In Russian). DOI:10.33266/1024-6177-2024-69-4-13-19
References
1. Бушманов А.Ю., Шейно И.Н., Липенгольц А.А., Соловьев А.Н., Корякин С.Н. Перспективы применения комбинированных технологий в протонной терапии злокачественных новообразований // Медицинская радиология и радиационная безопасность. 2019. Т. 64, № 3. С. 11–18 [Bushmanov АYu, Sheino IN, Lipengolts АА, Soloviev AN, Koryakin SN. Prospects of Proton Therapy Combined Technologies in the Treatment of Cancer. Medical Radiology and Radiation Safety. 2019;64(3):11–18 (In Russ.)]. DOI: 10.12737/article_5cf237bf846b67.57514871
2. Peukert D, Kempson I, Douglass M, Bezak E. Gold Nanoparticle Enhanced Proton Therapy: a Monte Carlo Simulation of the Effects of Proton Energy, Nanoparticle Size, Coating Material, and Coating Thickness on Dose and Radiolysis Yield. Med Phys. 2020; 47(2):651-661. DOI: 10.1002/mp.13923. PMID: 31725910
3. Benn TM, Westerhoff P. Nanoparticle Silver Released into Water from Commercially Available Sock Fabrics. Environ Sci Technol. 2008;42(11):4133-9. Erratum in: Environ Sci Technol. 2008; 42(18):7025-6. DOI: 10.1021/es7032718. PMID: 18589977
4. Petersen EJ, Pinto RA, Mai DJ, Landrum PF, Weber WJ Jr. Influence of Polyethyleneimine Graftings of Multi-Walled Carbon Nanotubes on their Accumulation and Elimination by and Toxicity to Daphnia Magna. Environ Sci Technol. 2011;45(3):1133-8. DOI: 10.1021/es1030239. PMID: 21182278.
5. Baun A, Hartmann NB, Grieger K, Kusk KO. Ecotoxicity of Engineered Nanoparticles to Aquatic Invertebrates: a Brief Review and Recommendations for Future Toxicity Testing. Ecotoxicology. 2008;17(5):387-95. DOI: 10.1007/s10646-008-0208-y. PMID: 18425578
6. Fuller N., Lerebours A., Smith J.T., Ford A.T. The Biological Effects of Ionising Radiation on Crustaceans: a Review. Aquat. Toxicol. 2015;167:55–67. http://dx.doi. org/10.1016/j.aquatox.2015.07.013
7. Feswick A, Griffitt RJ, Siebein K, Barber DS. Uptake, Retention and Internalization of Quantum Dots in Daphnia is Influenced by Particle Surface Functionalization. Aquat Toxicol. 2013;130-131:210-8. DOI: 10.1016/j.aquatox.2013.01.002. PMID: 23419536.
8. Liu A, Ye B. Application of Gold Nanoparticles in Biomedical Researches and Diagnosis. Clin Lab. 2013;59(1-2):23-36. PMID: 23505903.
9. Финогенова Ю.А., Липенгольц А.А., Скрибицкий В.А., Шпакова К.Е., Смирнова А.В., Скрибицкая А.В., Сычева Н.Н., Григорьева Е.Ю. Металлсодержащие наноразмерные радиосенсибилизаторы для лучевой терапии злокачественных новообразований // Медицинская физика, 2023.
№ 3. С 70-86 [Finogenova YA, Lipengolts AA, Skribitskiy VA, Shpakova KE, Smirnova AV, Skribitskaya AV, Sycheva NN, Grigorieva EY. Metal Nanoparticles as Radiosensitizers for Cancer Radiotherapy in Vivo. Meditsinskaya Fizika = Medical Physics, 2023;3:70-86 (In Russ.)]. DOI: 10.52775/1810-200x-2023-99-3-70-86
10. Скрибицкий В.А., Позднякова Н.В., Липенгольц А.А., Попов А.А., Тихоновский Г.В., Финогенова Ю.А., Смирнова А.В., Григорьева Е.Ю. Спектрофотометрический метод оценки размера и концентрации лазерно-аблированных золотых наночастиц // Биофизика. 2022. Т. 67, № 1. С. 30–36 [Skribitskiy VA, Pozdnyakova NV, Lipengolts AA, Popov AA, Tikhonovskiy GV, Finogenova YuA, Smirnova AV, Grigorieva EYu. A Spectrophotometric Method for Evaluation of Size and Concentration of Laser Ablated Gold Nanoparticles. Biofizika = Biophisics. 67(1):30–36 (In Russ.)]. DOI: 10.31857/S0006302922010045.
11. Test Guideline. Daphnia Magna Reproduction Test. OECD Guideline for the Testing of Chemicals. Paris, OECD Publ., 2012. No. 211. P. 26. http://dx.doi.org/10.1787/20745761.
12. Cancer Cell Culture. Methods and Protocols / Ed. I.A.Cree. New York, Dordrecht, Heidelberg, London, Springer, Human Press, 2011. P. 237-244.
13. Gorfine M, Schlesinger M, Hsu L. K-Sample Omnibus Non-Proportional Hazards Tests Based on Right-Censored Data. Stat Methods Med Res. 2020;29(10):2830-2850. doi: 10.1177/0962280220907355
14. Li S, Penninckx S, Karmani L, Heuskin AC, Watillon K, Marega R, Zola J, Corvaglia V, Genard G, Gallez B, Feron O, Martinive P, Bonifazi D, Michiels C, Lucas S. LET-Dependent Radiosensitization Effects of Gold Nanoparticles for Proton Irradiation. Nanotechnology. 2016;27(45):455101. Epub 2016 Oct 3. DOI: 10.1088/0957-4484/27/45/455101. PMID: 27694702
15. Kim JK, Seo SJ, Kim HT, Kim KH, Chung MH, Kim KR, et al. Enhanced Proton Treatment in Mouse Tumors Through Proton Irradiated Nanoradiator Effects on Metallic Nanoparticles. Phys Med Biol. 2012;57(24):8309-23. DOI: 10.1088/0031-9155/57/24/8309
16. Cunningham C, de Kock M, Engelbrecht M, Miles X, Slabbert J, Vandevoorde C. Radiosensitization Effect of Gold Nanoparticles in Proton Therapy. Front Public Health. 2021;9:699822. DOI: 10.3389/fpubh.2021.699822. PMID: 34395371; PMCID: PMC8358148
17. Sarapultseva EI, Dubrova YE. The Long-Term Effects of Acute Exposure to Ionising Radiation on Survival and Fertility in Daphnia Magna. Environ Res. 2016;150:138-143. doi: 10.1016/j.envres.2016.05.046. PMID: 27288911.
18. Nakamori T, Yoshida S, Kubota Y, Ban-nai T, Kaneko N, Hasegawa M, Itoh R. Effects of Acute Gamma Irradiation on Folsomia Candida (Collembola) in a Standard Test. Ecotoxicol Environ Saf. 2008;71(2):590-6. DOI: 10.1016/j.ecoenv.2007.10.029. PMID: 18155145
19. Won EJ, Lee JS. Gamma Radiation Induces Growth Retardation, Impaired Egg Production, and Oxidative Stress in the Marine Copepod Paracyclopina Nana. Aquat Toxicol. 2014;150:17-26. DOI: 10.1016/j.aquatox.2014.02.010. PMID: 24632311
20. Jönsson K.I. Radiation Tolerance in Tardigrades: Current Knowledge and Potential Applications in Medicine. Cancers 2019;11(9):1333; https://doi.org/10.3390/cancers11091333.
21. Dubrova YE, Sarapultseva EI. Radiation-Induced Transgenerational Effects in Animals. Int J Radiat Biol. 2022;98(6):1047-1053. DOI: 10.1080/09553002.2020.1793027. PMID: 32658553.
22. Min H, Sung M, Son M, Kawasaki I, Shim YH. Transgenerational Effects of Proton Beam Irradiation on Caenorhabditis Elegans Germline Apoptosis. Biochem Biophys Res Commun. 2017;490(3):608-615. DOI: 10.1016/j.bbrc.2017.06.085. PMID: 28630005.
23. Hoppe BS, Harris S, Rhoton-Vlasak A, Bryant C, Morris CG, Dagan R, Nichols RC, Mendenhall WM, Henderson RH, Li Z, Mendenhall NP. Sperm Preservation and Neutron Contamination Following Proton Therapy for Prostate Cancer Study. Acta Oncol. 2017;56(1):17-20. DOI: 10.1080/0284186X.2016.1205219. PMID: 27420031
24. Wo JY, Viswanathan AN. The Impact of Radiotherapy on Fertility, Pregnancy, and Neonatal Outcomes in Female Cancer Patients. Int J Radiat Oncol Biol Phys. 2009;73:1304–1312. doi: 10.1016/j.ijrobp.2008.12.016.
25. Streffer C, Shore R, Konermann G, Meadows A, Uma Devi P, Preston Withers J, Holm LE, Stather J, Mabuchi K, H R. Biological Effects after Prenatal Irradiation (Embryo and Fetus). A Report of the International Commission on Radiological Protection. Ann ICRP. 2003;33(1-2):5-206. PMID: 12963090.
26. Falk M. Nanodiamonds and Nanoparticles as Tumor Cell Radiosensitizers-Promising Results but an Obscure Mechanism of Action. Ann Transl Med. 2017;5(1):18. DOI: 10.21037/atm.2016.12.62. PMID: 28164103; PMCID: PMC5253274
27. Hainfeld JF, Dilmanian FA, Zhong Z, Slatkin DN, Kalef-Ezra JA, Smilowitz HM. Gold Nanoparticles Enhance the Radiation Therapy of a Murine Squamous Cell Carcinoma. Phys Med Biol. 2010;55(11):3045-59. DOI: 10.1088/0031-9155/55/11/004. PMID: 20463371
28. Ates M, Danabas D, Ertit Tastan B, Unal I, Cicek Cimen IC, Aksu O, Kutlu B, Arslan Z. Assessment of Oxidative Stress on Artemia salina and Daphnia magna After Exposure to Zn and ZnO Nanoparticles. Bull Environ Contam Toxicol. 2020; 104(2):206-214. doi: 10.1007/s00128-019-02751-6. PMID: 31748865.
PDF (RUS) Full-text article (in Russian)
Conflict of interest. The authors declare no conflict of interest.
Financing. The work was carried out with the financial support of the Russian Academy of Sciences within the framework of scientific project No. 23-24-10041. The irradiation was carried out on the equipment of the Central Research Center «Radiological and Cellular Technologies» of the Federal State Budgetary Institution «NMIC Radiology» of the Ministry of Health of the Russian Federation.
Contribution. Article was prepared with equal participation of the authors.
Article received: 20.03.2024. Accepted for publication: 25.04.2024.