Binary proton therapy of Ehrlich carcinoma using targeted gold nanoparticles

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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.

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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; Obninsk

D. 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, Obninsk

O. 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, Obninsk

A. 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, Obninsk

V. 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, Obninsk

A. 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, Obninsk

K. 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, Obninsk

G. 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, Obninsk

A. 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; Obninsk

S. M. Deyev

Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: d.petrunya@lebedev.ru

Academician of the RAS

Russian Federation, Moscow

I. 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

  1. 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
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. Tolmachev V.M., Chernov V.I., Deyev S.M. Targeted Nuclear Medicine. Seek and Destroy // Russ. Chem. Rev. 2022. V. 91(3). RCR5034.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. 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.

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2. Fig. 1. Transmission electron microscopy image of Au nanoparticles.

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3. Fig. 2. Clonogenic analysis of EMT6/P adenocarcinoma cells after proton beam irradiation in the presence of Au-PEG nanoparticles. * – p < 0.05, ** – p < 0.001, Student’s t-test.

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4. Fig. 3. Growth inhibition index (GI) values ​​of Ehrlich carcinoma after proton irradiation at a dose of 31 Gy in the presence and absence of Au-PEG-FA nanoparticles. * – p < 0.05, Kruskal–Wallis test.

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