Binary proton therapy of Ehrlich carcinoma using targeted gold nanoparticles
- Authors: Filimonova M.V.1,2, Kolmanovich D.D.3,4, Tikhonowski G.V.2, Petrunya D.S.4,2, Kotelnikova P.A.5, Shitova A.A.1, Soldatova O.V.1, Filimonov A.S.1, Rybachuk V.A.1, Kosachenko A.O.1, Nikolaev K.A.1, Demyashkin G.A.1, Popov A.A.2, Savinov M.S.2, Popov A.L.3,4, Zelepukin I.V.5, Lipengolts A.A.2,6, Shpakova K.E.2,6, Kabashin A.V.7, Koryakin S.N.1,2, Deyev S.M.5, Zavestovskaya I.N.4,2
-
Affiliations:
- National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation
- National Research Nuclear University MEPhI (Moscow Engineering Physics Institute)
- Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences
- P.N. Lebedev Physical Institute of the Russian Academy of Sciences
- Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
- Institution N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation
- Aix-Marseille University
- Issue: Vol 516, No 1 (2024)
- Pages: 59-63
- Section: Articles
- URL: https://cijournal.ru/2686-7389/article/view/651431
- DOI: https://doi.org/10.31857/S2686738924030104
- EDN: https://elibrary.ru/VTOKHA
- ID: 651431
Cite item
Abstract
Proton therapy can treat tumors located in radiation-sensitive tissues. This article demonstrates the possibility of enhancing the proton therapy with targeted gold nanoparticles that selectively recognize tumor cells. Au-PEG nanoparticles at concentrations above 25 mg/L and 4 Gy proton dose caused complete death of EMT6/P cells in vitro. Binary proton therapy using targeted Au-PEG-FA nanoparticles caused an 80% tumor growth inhibition effect in vivo. The use of targeted gold nanoparticles is promising for enhancing the proton irradiation effect on tumor cells and requires further research to increase the therapeutic index of the approach.
Keywords
Full Text

About the authors
M. V. Filimonova
National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation; National Research Nuclear University MEPhI (Moscow Engineering Physics Institute)
Email: d.petrunya@lebedev.ru
A. Tsyb Medical Radiological Research Centre, Obninsk Institute for Nuclear Power Engineering
Russian Federation, Obninsk; ObninskD. D. Kolmanovich
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences; P.N. Lebedev Physical Institute of the Russian Academy of Sciences
Email: d.petrunya@lebedev.ru
Russian Federation, Pushchino; Moscow
G. V. Tikhonowski
National Research Nuclear University MEPhI (Moscow Engineering Physics Institute)
Email: d.petrunya@lebedev.ru
Russian Federation, Moscow
D. S. Petrunya
P.N. Lebedev Physical Institute of the Russian Academy of Sciences; National Research Nuclear University MEPhI (Moscow Engineering Physics Institute)
Author for correspondence.
Email: d.petrunya@lebedev.ru
Russian Federation, Moscow; Moscow
P. A. Kotelnikova
Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
Email: d.petrunya@lebedev.ru
Russian Federation, Moscow
A. A. Shitova
National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation
Email: d.petrunya@lebedev.ru
A. Tsyb Medical Radiological Research Centre
Russian Federation, ObninskO. V. Soldatova
National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation
Email: d.petrunya@lebedev.ru
A. Tsyb Medical Radiological Research Centre
Russian Federation, ObninskA. S. Filimonov
National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation
Email: d.petrunya@lebedev.ru
A. Tsyb Medical Radiological Research Centre
Russian Federation, ObninskV. A. Rybachuk
National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation
Email: d.petrunya@lebedev.ru
A. Tsyb Medical Radiological Research Centre
Russian Federation, ObninskA. O. Kosachenko
National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation
Email: d.petrunya@lebedev.ru
A. Tsyb Medical Radiological Research Centre
Russian Federation, ObninskK. A. Nikolaev
National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation
Email: d.petrunya@lebedev.ru
A. Tsyb Medical Radiological Research Centre
Russian Federation, ObninskG. A. Demyashkin
National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation
Email: d.petrunya@lebedev.ru
A. Tsyb Medical Radiological Research Centre
Russian Federation, ObninskA. A. Popov
National Research Nuclear University MEPhI (Moscow Engineering Physics Institute)
Email: d.petrunya@lebedev.ru
Russian Federation, Moscow
M. S. Savinov
National Research Nuclear University MEPhI (Moscow Engineering Physics Institute)
Email: d.petrunya@lebedev.ru
Russian Federation, Moscow
A. L. Popov
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences; P.N. Lebedev Physical Institute of the Russian Academy of Sciences
Email: d.petrunya@lebedev.ru
Russian Federation, Pushchino; Moscow
I. V. Zelepukin
Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
Email: d.petrunya@lebedev.ru
Russian Federation, Moscow
A. A. Lipengolts
National Research Nuclear University MEPhI (Moscow Engineering Physics Institute); Institution N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation
Email: d.petrunya@lebedev.ru
Russian Federation, Moscow; Moscow
K. E. Shpakova
National Research Nuclear University MEPhI (Moscow Engineering Physics Institute); Institution N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation
Email: d.petrunya@lebedev.ru
Russian Federation, Moscow; Moscow
A. V. Kabashin
Aix-Marseille University
Email: d.petrunya@lebedev.ru
France, Marseille
S. N. Koryakin
National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation; National Research Nuclear University MEPhI (Moscow Engineering Physics Institute)
Email: d.petrunya@lebedev.ru
A. Tsyb Medical Radiological Research Centre, Obninsk Institute for Nuclear Power Engineering
Russian Federation, Obninsk; ObninskS. M. Deyev
Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
Email: d.petrunya@lebedev.ru
Academician of the RAS
Russian Federation, MoscowI. N. Zavestovskaya
P.N. Lebedev Physical Institute of the Russian Academy of Sciences; National Research Nuclear University MEPhI (Moscow Engineering Physics Institute)
Email: d.petrunya@lebedev.ru
Russian Federation, Moscow; Moscow
References
- Durante M., Loeffler J.S. Charged Particles in Radiation Oncology // Nat. Rev. Clin. Oncol. 2010. V. 7(1). P. 37–43. https://doi.org/10.1038/nrclinonc.2009.183
- Lo C.Y., Tsai S.W., Niu H., et al. Gold-nanoparticles-enhanced Production of Reactive Oxygen Species in Cells at Spread-out Bragg Peak under Proton Beam Radiation // ACS Omega. 2023. V. 8(20). P. 17922–17931.
- Martínez‐Rovira I., Prezado Y. Evaluation of the Local Dose Enhancement in the Combination of Proton Therapy and Nanoparticles // Med. Phys. 2015. V. 42(11). P. 6703–6710.
- Zwiehoff S., Johny J., Behrends C., et al. Enhancement of Proton Therapy Efficiency by Noble Metal Nanoparticles is Driven by the Number and Chemical Activity of Surface Atoms // Small. 2022. V. 18(9). P. e2106383.
- Zavestovskaya I.N., Popov A.L., Kolmanovich D.D., et al. Boron Nanoparticle-enhanced Proton Therapy for Cancer Treatment // Nanomaterials (Basel). 2023. V. 13(15). P. 2167.
- Gerken L.R.H., Gogos A., Starsich F.H.L., et al. Catalytic Activity Imperative for Nanoparticle Dose Enhancement in Photon and Proton Therapy // Nat. Commun. 2022. V. 13(1). 3248.
- Zelepukin I.V., Griaznova O.Yu., Shevchenko K.G., et al. Flash Drug Release from Nanoparticles Accumulated in the Targeted Blood Vessels facilitates the Tumour Treatment // Nat. Commun. 2022. V. 13(1). 6910.
- Tolmachev V.M., Chernov V.I., Deyev S.M. Targeted Nuclear Medicine. Seek and Destroy // Russ. Chem. Rev. 2022. V. 91(3). RCR5034.
- Li S., Bouchy S., Penninckx S., Marega R., et al. Antibody-functionalized Gold Nanoparticles as Tumor Targeting Radiosensitizers for Proton Therapy // Nanomedicine. 2019. V. 14(3). P. 317–333.
- Kang S.H., Hong S.P., Kang B.S. Targeting Chemo-proton Therapy on C6 Cell Line Using Superparamagnetic Iron Oxide Nanoparticles Conjugated with Folate and Paclitaxel // International Journal of Radiation Biology. 2018. V. 94(11). P. 1006–1016.
- Siwowska K., Haller S., Bortoli F., et al. Preclinical Comparison of Albumin-binding Radiofolates: Impact of Linker Entities on the in Vitro and in Vivo Properties // Mol. Pharm. 2017. V. 14(2). P. 523–532.
- Popov A.A., Swiatkowska-Warkocka Z., Marszalek M., et al. Laser-ablative Synthesis of Ultrapure Magneto-plasmonic Core-satellite Nanocomposites for Biomedical Applications // Nanomaterials (Basel). 2022. V. 12(4). 649.
- Gao J., Huang X., Liu H., Zan F., Ren J. Colloidal Stability of Gold Nanoparticles Modified with Thiol Compounds: Bioconjugation and Application in Cancer Cell Imaging // Langmuir. 2012. V. 28(9). P. 4464–4471.
- R S., M Joseph M., Sen A., K R.P., Bs U., Tt S. Galactomannan Armed Superparamagnetic Iron Oxide Nanoparticles as a Folate Receptor Targeted Multi-functional Theranostic Agent in the Management of Cancer // Int. J. Biol. Macromol. 2022. V. 219. P. 740–753.
- Baibarac M., Smaranda I., Nila A., Serbschi C. Optical Properties of Folic Acid in Phosphate Buffer Solutions: The Influence of pH and UV Irradiation on the UV–VIS Absorption Spectra and Photoluminescence // Sci. Rep. 2019. V. 9(1). 14278.
- Filimonova M., Shitova A., Soldatova O., et al. Combination of NOS- and PDK-Inhibitory Activity: Possible Way to Enhance Antitumor Effects // Int. J. Mol. Sci. 2022. V. 23. 730.
Supplementary files
