Синтез редокс-активных наночастиц Ce_0.75Bi_0.15Tb_0.1F₃ и исследование их биосовместимости in vitro

Наночастицы фторида церия (CeF₃), являясь уникальным нанозимом и редокс-активным наноматериалом, демонстрируют перспективные возможности их использования для передовых биомедицинских применений. Легирование наночастиц CeF₃ другими химическими элементами позволяет повысить их каталитическую активность, придать им новые функциональные свойства, а также повысить эффективность их взаимодействия с ионизирующим излучением, что важно при разработке новых нанорадиосенсибилизаторов. В этой статье мы синтезировали цитрат-стабилизированные наночастицы Ce_0.75Bi_0.15Tb_0.1F₃, которые демонстрируют высокую коллоидную стабильность, обладают хорошими люминесцентными свойствами и радиационно-индуцированной окислительно-восстановительной активностью. Анализ цитотоксичности наночастиц Ce_0.75Bi_0.15Tb_0.1F₃ на культурах нормальных и опухолевых клеток in vitro показал чувствительность линий опухолевых клеток (B16/F10 и EMTP6) к наночастицам в высоких концентрациях (0,5-1 мМ). Полученные экспериментальные результаты позволяют рассматривать наночастицы Ce_0.75Bi_0.15Tb_0.1F₃ в качестве возможной платформы для разработки нового класса нанорадиосенсибилизаторов для целей лучевой терапии.

1. Tang J.L.Y., Moonshi S.S., Ta H.T. Nanoceria: An Innovative Strategy for Cancer Treatment. Cell. Mol. Life Sci., 2023, 80, 46.

2. Li H., Xia P., Pan S., Qi Z., Fu C., Yu Z., Kong W., Chang Y., Wang K., Wu D., et al. The Advances of Ceria Nanoparticles for Biomedical Applications in Orthopaedics. Int. J. Nanomedicine, 2020, 15, P. 7199–7214.

3. Garzón-Manjón A., Aranda-Ramos A., Melara-Benítez B., Bensarghin I., Ros J., Ricart S., Nogués C. Simple Synthesis of Biocompatible Stable CeO2 Nanoparticles as Antioxidant Agents. Bioconjug. Chem., 2018, 29, P. 2325–2331.

4. Banavar S., Deshpande A., Sur S., Andreescu S. Ceria Nanoparticle Theranostics: Harnessing Antioxidant Properties in Biomedicine and Beyond. J. Phys. Mater., 2021, 4, 042003

5. Popov A.L., Shcherbakov A.B., Zholobak N.M., Baranchikov A.E., Ivanov V.K. Cerium Dioxide Nanoparticles as Third-Generation Enzymes (Nanozymes). Nanosyst. Phys. Chem. Math., 2017, 8 (6), P. 760–781.

6. Liu H., Liu J. Self-Limited Phosphatase-Mimicking CeO2 Nanozymes. ChemNanoMat, 2020, 6, P. 947–952.

7. Ma Y., Tian Z., Zhai W., Qu Y. Insights on Catalytic Mechanism of CeO2 as Multiple Nanozymes. Nano Res., 2022, 15, P. 10328–10342.

8. Luo Q., Li Y., Huo X., Li J., Li L., Wang W., Li Y., Chen S., Song Y., Wang N. Stabilizing Ultrasmall Ceria-Cluster Nanozyme for Antibacterial and Antibiofouling Applications. Small, 2022, 18, 2107401.

9. Nelson B.C., Johnson M.E., Walker M.L., Riley K.R., Sims C.M. Antioxidant Cerium Oxide Nanoparticles in Biology and Medicine. Antioxidants, 2016 5, 15.

10. Chukavin N.N., Filippova K.O., Ermakov A.M., Karmanova E.E., Popova N.R., Anikina V.A., Ivanova O.S., Ivanov V.K., Popov A.L. Redox-Active Cerium Fluoride Nanoparticles Selectively Modulate Cellular Response against X-Ray Irradiation In Vitro. Biomedicines, 2024, 12, 11.

11. Ermakov A., Popov A., Ermakova O., Ivanova O., Baranchikov A., Kamenskikh K., Shekunova T., Shcherbakov A., Popova N., Ivanov V. The First Inorganic Mitogens: Cerium Oxide and Cerium Fluoride Nanoparticles Stimulate Planarian Regeneration via Neoblastic Activation. Mater. Sci. Eng. C, 2019, 104, 109924.

12. Filippova K.O., Ermakov A.M., Popov A.L., Ermakova O.N., Blagodatsky A.S., Chukavin N.N., Shcherbakov A.B., Baranchikov A.E., Ivanov V.K. Mitogen-like Cerium-Based Nanoparticles Protect Schmidtea Mediterranea against Severe Doses of X-Rays. Int. J. Mol. Sci., 2023, 24, 1241.

13. Jacobsohn L.G., Kucera C.J., James T.L., Sprinkle K.B., DiMaio J.R., Kokuoz B., Yazgan-Kukouz B., DeVol T.A., Ballato J. Preparation and Characterization of Rare Earth Doped Fluoride Nanoparticles. Materials, 2010, 3, P. 2053–2068.

14. Secco H. de L., Ferreira F.F., Péres L.O. Simple Preparation of Fluorescent Composite Films Based on Cerium and Europium Doped LaF3 Nanoparticles. J. Solid State Chem., 2018, 259, P. 43–47.

15. Huong D.T.M., Tien N.T., Vu L.V., Long N.N. Synthesis and Optical Characterization of Samarium Doped Cerium Fluoride Nanoparticles. VNU J. Sci. Math.-Phys., 2015, 31.

16. Greis O., Haschke J.M. Rare Earth Fluorides. In Handbook on the Physics and Chemistry of Rare Earths, Elsevier, 1982, 5, P. 387–460.

17. Pudovkin M.S., Morozov O.A., Korableva S.L., Rakhmatullin R.M., Semashko V.V., Ginkel A.K., Rodionov A.A., Kiiamov A.G. EPR and Optical Study of Erbium-Doped CeO2 and CeO2/CeF3 Nanoparticles. Ceram. Int., 2024, 50, P. 9263–9269.

18. Cheng Y., Xu H., Cao W., Gao W., Tang B. Cerium Fluoride Nanoparticles as a Theranostic Material for Optical Imaging of Vulnerable Atherosclerosis Plaques. J. Am. Ceram. Soc., 2023, 106, P. 2375–2383.

19. Wang J., Ansari A.A., Malik A., Syed R., Ola M.S., Kumar A., AlGhamdi K.M., Khan S. Highly Water-Soluble Luminescent Silica-Coated Cerium Fluoride Nanoparticles Synthesis, Characterizations, and In Vitro Evaluation of Possible Cytotoxicity. ACS Omega, 2020, 5, P. 19174–19180.

20. Cooper D.R., Kudinov K., Tyagi P., Hill C.K., Bradforth S.E., Nadeau J.L. Photoluminescence of Cerium Fluoride and Cerium-Doped Lanthanum Fluoride Nanoparticles and Investigation of Energy Transfer to Photosensitizer Molecules. Phys. Chem. Chem. Phys., 2014, 16, P. 12441–12453.

21. Gerken L.R.H., Gerdes M.E., Pruschy M., Herrmann I.K. Prospects of Nanoparticle-Based Radioenhancement for Radiotherapy. Mater. Horiz., 2023, 10, P. 4059–4082.

22. Deng J., Xu S., Hu W., Xun X., Zheng L., Su M. Tumor Targeted Stealthy and Degradable Bismuth Nanoparticles for Enhanced X-Ray Radiation Therapy of Breast Cancer. Biomaterials, 2018, 154, P. 24–33.

23. Fan W., Tang W., Lau J., Shen Z., Xie J., Shi J., Chen X. Breaking the Depth Dependence by Nanotechnology-Enhanced X-Ray-Excited Deep Cancer Theranostics. Adv. Mater., 2019, 31, 1806381.

24. Yuan Z., Liu X., Ling J., Huang G., Huang J., Zhu X., He L., Chen T. In Situ-Transition Nanozyme Triggered by Tumor Microenvironment Boosts Synergistic Cancer Radio-/Chemotherapy through Disrupting Redox Homeostasis. Biomaterials, 2022, 287, 121620.

25. Liu S., Fang L., Ding H., Zhang Y., Li W., Liu B., Dong S., Tian B., Feng L., Yang P. Alternative Strategy to Optimize Cerium Oxide for Enhanced X-Ray-Induced Photodynamic Therapy. ACS Nano, 2022, 16, P. 20805–20819.

26. Zhu X., Wu J., Liu R., Xiang H., Zhang W., Chang Q., Wang S., Jiang R., Zhao F., Li Q., et al. Engineering Single-Atom Iron Nanozymes with Radiation-Enhanced Self-Cascade Catalysis and Self-Supplied H2O2 for Radio-Enzymatic Therapy. ACS Nano, 2022, 16, P. 18849–18862.

27. Bagley A.F., Ludmir E.B., Maitra A., Minsky B.D., Li Smith G., Das P., Koong A.C., Holliday E.B., Taniguchi C.M., Katz M.H.G., et al. NBTXR3, a First-in-Class Radioenhancer for Pancreatic Ductal Adenocarcinoma: Report of First Patient Experience. Clin. Transl. Radiat. Oncol., 2022, 33, P. 66–69.

28. Lux F., Tran V.L., Thomas E., Dufort S., Rossetti F., Martini M., Truillet C., Doussineau T., Bort G., Denat F., et al. AGuIX® from Bench to Bedside-Transfer of an Ultrasmall Theranostic Gadolinium-Based Nanoparticle to Clinical Medicine. Br. J. Radiol., 2019, 92, 20180365.

29. Ghasemi M., Turnbull T., Sebastian S., Kempson I. The MTT Assay: Utility, Limitations, Pitfalls, and Interpretation in Bulk and Single-Cell Analysis. Int. J. Mol. Sci., 2021, 22, 12827.

30. Aplak E., Montfort C. von, Haasler L., Stucki D., Steckel B., Reichert A.S., Stahl W., Brenneisen P. CNP Mediated Selective Toxicity on Melanoma Cells Is Accompanied by Mitochondrial Dysfunction. PLOS ONE, 2020, 15, e0227926.

31. Kolmanovich D.D., Chukavin N.N., Savintseva I.V., Mysina E.A., Popova N.R., Baranchikov A.E., Sozarukova M.M., Ivanov V.K., Popov A.L. Hybrid Polyelectrolyte Capsules Loaded with Gadolinium-Doped Cerium Oxide Nanoparticles as a Biocompatible MRI Agent for Theranostic Applications. Polymers, 2023, 15, 3840.