najoNanosystems: Physics, Chemistry, MathematicsНаносистемы: физика, химия, математика2220-80542305-7971Университет ИТМО10.17586/2220-8054-2024-15-5-675-682najo-138Research ArticleCHEMISTRY AND MATERIAL SCIENCEХИМИЯ И МАТЕРИАЛОВЕДЕНИЕProton beam-induced radiosensitizing effect of Ce0.8Gd0.2O2−x nanoparticles against melanoma cells in vitroИндуцированный пучком протонов радиосенсибилизирующий эффект наночастиц Ce0.8Gd0.2O2-x в отношении клеток меланомы in vitrohttps://orcid.org/0000-0003-3391-7889КолмановичД. Д.KolmanovichDanil D.

Данил Денисович Колманович

Danil D. Kolmanovich

Pushchino

kdd100996@mail.ruhttps://orcid.org/0009-0005-8700-1536РомановМ. В.RomanovMikhail V.

Михаил Вячеславович Романов

Mikhail V. Romanov

Moscow

https://orcid.org/0000-0001-9286-3644ХаустовС. А.KhaustovSergey A.

Сергей Анатольевич Хаустов

Sergey A. Khaustov

Moscow

https://orcid.org/0000-0003-2343-2140ИвановВ. И.IvanovVladimir K.

Владимир Константинович Иванов

Vladimir K. Ivanov

Moscow

van@igic.ras.ruhttps://orcid.org/0000-0003-1175-6703ШемяковА. Е.ShemyakovAlexander E.

Александр Евгеньевич Шемяков

Alexander E. Shemyakov

Pushchino; Moscow

alshemyakov@yandex.ruhttps://orcid.org/0000-0001-8431-4485ЧукавинН. Н.ChukavinNikita N.

Чукавин Никита Николаевич

Nikita N. Chukavin

Pushchino; Moscow

chukavinnik@gmail.comhttps://orcid.org/0000-0003-2643-4846ПоповА. Л.PopovAnton L.

Антон Леонидович Попов 

Anton L. Popov

Pushchino; Moscow

antonpopovleonid@gmail.comInstitute of Theoretical and Experimental Biophysics of the Russian Academy of SciencesRussian FederationInstitute of Molecular Theranostics, Sechenov First Moscow State Medical University; Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological AgencyRussian FederationScientific and Educational Center, State University of EducationRussian FederationKurnakov Institute of General and Inorganic Chemistry of the Russian Academy of SciencesRussian FederationInstitute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences; Lebedev Physical Institute of the Russian Academy of SciencesRussian FederationInstitute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences;Scientific and Educational Center, State University of EducationRussian FederationInstitute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences; Scientific and Educational Center, State University of EducationRussian Federation202403062025155675682Copyright © Kolmanovich D.D., Romanov M.V., Khaustov S.A., Ivanov V.K., Shemyakov A.E., Chukavin N.N., Popov A.L., 20252025Колманович Д.Д., Романов М.В., Хаустов С.А., Иванов В.И., Шемяков А.Е., Чукавин Н.Н., Попов А.Л.Kolmanovich D.D., Romanov M.V., Khaustov S.A., Ivanov V.K., Shemyakov A.E., Chukavin N.N., Popov A.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://nanojournal.ifmo.ru/jour/article/view/138

T Proton beam therapy is being used increasingly to treat melanoma. Meanwhile, proton beam therapy has a number of disadvantages that can be reduced or completely eliminated through the use of modern innovative approaches, including the use of nanoradiosensitizers. Here we showed the possibility of using redox-active dextran-stabilized Ce0,8Gd0,2O2−x nanoparticles (Ce0,8Gd0,2O2−x NPs) as a radiosensitizer to promote mouse melanoma cell death under proton beam irradiation in vitro. It has been shown that these Ce0,8Gd0,2O2−x NPs do not reduce the viability and survival rate of both NCTC L929 normal mouse fibroblasts and B16/F10 mouse melanoma cells in a wide range of concentrations. However, Ce0,8Gd0,2O2−x NPs significantly reduce the mitochondrial membrane potential of these cells. Additionally, it has been shown that Ce0,8Gd0,2O2−x NPs are able to effectively reduce the clonogenic activity of B16/F10 melanoma cells under proton beam irradiation. Meanwhile, proton beam irradiation remarkably reduced the clonogenic activity and MMP of melanoma cells. Hence, Ce0,8Gd0,2O2−x NPs act as a radiosensitizer in B16/F10 mouse melanoma cells under proton beam irradiation. We assume that such radiosensitizing effect of Ce0,8Gd0,2O2−x NPs is due to a decrease of the membrane mitochondrial potential. Thus, the use of Ce0,8Gd0,2O2−x NPs in combination with proton beam irradiation is a promising approach for the effective treatment of melanoma.

Протонно-лучевая терапия все чаще используется для лечения меланомы. Между тем, протонно-лучевая терапия имеет ряд недостатков, которые можно уменьшить или полностью устранить с помощью современных инновационных подходов, включая использование нанорадиосенсибилизаторов. Здесь мы показали возможность использования редокс-активных наночастиц Ce0,8Gd0,2O2-x, стабилизированных декстраном (Ce0,8Gd0,2O2-x НЧ) в качестве радиосенсибилизатора для стимулирования гибели клеток меланомы мыши при облучении пучком протонов in vitro. Было показано, что Ce0,8Gd0,2O2-x НЧ не снижают жизнеспособность и выживаемость как нормальных мышиных фибробластов NCTC L929, так и клеток мышиной меланомы B16/F10 в широком диапазоне концентраций. Однако Ce0,8Gd0,2O2-x НЧ значительно снижают мембранный потенциал митохондрий этих клеток. Кроме того, было показано, что Ce0,8Gd0,2O2-x НЧ способны эффективно снижать клоногенную активность клеток меланомы B16/F10 при облучении пучком протонов. Между тем, облучение протонным пучком значительно снижало клоногенную активность и ММР клеток меланомы. Следовательно, Ce0,8Gd0,2O2-x НЧ действуют как радиосенсибилизатор в клетках меланомы мыши B16/F10 при облучении пучком протонов. Мы предполагаем, что такой радиосенсибилизирующий эффект Ce0,8Gd0,2O2-x НЧ обусловлен гипополяризацией мембран митохондрий. Таким образом, использование Ce0,8Gd0,2O2-x НЧ в сочетании с облучением пучком протонов является перспективным подходом для эффективного лечения меланомы.

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The authors declare that there are no conflicts of interest present.