The efficiency of the photon capture therapy with gold containing compounds based on hyaluronic acid (experimental study)

«Radiation and Risk», 2017, vol. 26, No. 2, pp.49-61

DOI: 10.21870/0131-3878-2017-26-2-49-61

Authors

Koryakin S.N.1 – Head of Lab., C. Sc., Biol. A. Tsyb MRRC. Contacts: 4 Korolev str., Obninsk, Kaluga region, Russia, 249036. Tel.: (484) 399-72-76, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. .
Ulyanenko S.E.1 – Head of Dep., D. Sc., Biol. A. Tsyb MRRC.
Isaeva E.V.1 – Sen. Res., C. Sc., Vet. A. Tsyb MRRC.
Beketov E.E.1 – Head of Lab., C. Sc., Biol. A. Tsyb MRRC.
Ulyanenko L.N.1 – Lead. Res., D. Sc., Biol. A. Tsyb MRRC. Uspenskiy S.A.2,3 – Sen. Res., C. Sc., Chem. ISPM RAS.
Selyanin M.A.2 – President Martinex RC.
Zelenetskii A.N.3 – Head of Lab., D. Sc., Chem. Enikolopov Institute of Synthetic Polymeric Materials of RAS (ISPM RAS), Moscow.

Abstract

The efficiency of the photon capture therapy with synthesized gold-containing nanocomposite for experimental sarcoma M-1 was estimated. To simulate photon capture irradiation the animals were exposed to single X-ray dose of 28 Gy delivered to the tumor following administration of a single dose of gold-containing compound based on hyaluronic acid and melanin. The composite was injected intratumorally in the amount of 4 mg of gold per animal 15 minutes before irradiation. Dynamic curves of tumor growth for 27 days after X-ray exposure of rats with the injected gold com-posite were similar to tumor growth curves after single local X-ray exposure to 32 Gy. The absorbed dose reduction due to photon-capturing events was 4 Gy (about 14%). Efficiency of experimental photon capture therapy was estimated by comparison of tumor growth inhibition indexes. The experimental photon-capture therapy was by 26% more efficient than local acute X-rays irradiation. No significant difference in skin reactions yield was observed. The obtained results showed the gold-containing nanocomposite based on hyaluronic acid and melanin to be promising agent for photon-capture therapy. The observed difference between therapeutic efficiency estimates due to the use of different criteria, such as relative tumor volume, tumor growth inhibition index, tumor growth factor, irradiation efficiency ratio, skin reactions yield, highlights the need to develop a multi-faceted approach for creating the medical technology.

Key words
Photon-capture therapy, X-ray, gold compound, nanoparticles, hyaluronic acid, melanin, rats with sarcoma M-1, intratumoral administration, absorbed dose, anti-tumor efficiency, skin reaction yield.

References

1. Davidov M.I., Golan A.V., Kanaev S.V., Kostilev V.A., Matyakin G.G., Mardinsky Yu.S., Panshin G.A., Tkachev S.I., Chmielewski E.V., Yur’eva T.V. Analiz sostoyania I koncepciya modernizacii radiacionnoi onkologii I medicinskoi fisiki [Analysis of the state and the concept of modernization of radiation oncology and medical physics. Voprosy onkologii – Questions of Oncology, 2013, vol. 59, no 5, pp. 529-538.

2. Kaprin A., Ulyanenko S. Adronnaya terapiya – tochki razvitiya [Hadron therapy – development point]. Medicina: celevye proekty – Medicine: targeted projects, 2016, no. 23. pp. 56-59.

3. Khokhlov V.F., Kulakov V.N., Shano I.N., Nasonova T.A., Mitin V.N., Dobrynina O.A. Sposob foton-zahvatnoi terapii opuholei [Method of photon-capture tumor therapy]. RF Patent № 2270045. Bul. № 5. 20.02.2004.

4. Kobayashi K., Usami N., Porcel E., Lacombe S., Le Sech C. Enhancement of radiation effect by heavy elements. Mutation Res., 2010, vol. 704, pp. 123-131.

5. Hohlov V.F., Izhevskij P.V., Kulakov V.N., Lipengolc A.A., Slobodjanik I.I., Fedotov Ju.A. Farmakokineticheskaja ocenka preparatov dlja binarnoj luchevoj terapii v ramkah skriningovogo issledovanija [Pharmacokinetic evaluation of drugs for binary radiation therapy as part of a screening study]. Rossijskij bioterapevticheskij zhurnal – Russian Biotherapeutic Journal, 2009. vol. 8, no. 1, pp. 25.

6. Cherepanov A.A., Lipengol'c A.A., Nasonova T.A., Dobrynina O.A., Kulakov V.N., Shejno I.N., Hohlov V.F., Klimanov V.A., Grigor'eva E.Ju. Uvelichenie protivoopuholevogo jeffekta rentgenovskogo obluchenija pri pomoshhi gadolinij soderzhashhego preparata na primere myshej s transplantiruemoj melanomoj B16F10 [The increase in the antitumor effect of X-ray irradiation using gadolinium-containing drug on mice with transplanted example melanoma B16F10]. Medicinskaja biofizika – Medical Biophysics, 2014, no. 3, pp. 66-69.

7. Rahman W.N., Bishara N., Ackerly T., He C.F., Jackson P., Wong C., Davidson R., Geso M. Enhancement of radiation effects by gold nanoparticles for superficial radiation therapy. Nanomedicine, 2009, vol. 5, pp. 136-142.

8. Koryakin S.N., Yadrovskaya V.A., Beketov E.E., Isaeva E.V., Ulyanenko S.E., Uspenskiy S.A., Khabarov V.N., Selyanin M.A. The study of hyaluronic acid compounds for neutron capture and photon ac-tivation therapies. Cent. Eur. J.Biol., 2014, vol. 9, no. 10, pp. 922-930.

9. Koryakin S.N., Ulyanenko S.E., Isaeva E.V., Beketov E.E., Yadrovskaya V.A., Uspenskiy S.A., Selyanin M.A. Ocenka citotoksichnosti I nakopleniya v opuholi zolotosoderzhachih soedinenii na osnove gialuronovoi kisloti [Evaluation of cytotoxicity and tumor accumulation of gold compounds on the basis of hyaluronic acid]. Radiatsiya i risk – Radiation and Risk, 2015, vol. 24, no 3, pp. 115-124.

10. Koryakin S.N., Isaeva E.V., Ulyanenko S.E., Beketov E.E., Troshina M.V., Yadrovskaya V.A. Izuchenie effectov foton-zahvatnoi terapii po testy klonogennoi aktivnosti kletok melanoma B-16 [Studying the effects of photon capture therapy on test clonogenic activity of cells melanoma B-16]. Proceedings of the regional competition of fundamental research projects. Kaluga, 2016, vol. 21, pp. 204-210.

11. X-5 Monte Carlo Team. MCNP – A General Monte Carlo N-Particle Transport Code, Version 5. Volume I: Overview and Theory, LA-UR-03-1987, 2005.

12. Ulyanenko S.E., Soloviev A.N., Lityaev V.M., Fedorov V.V., Koryakin S.N. Matematicheskoe modelirovanie foton I proton-zachvatnoi terapii s ispolzovaniem prepatatov zolota [Mathematical modeling of photon and proton-capture therapy using gold preparations]. Medicinskaja radiologija i radiacionnaja bezopasnost' – Nuclear Medicine and Radiation Safety, 2016, no. 5, pp. 59-64.

13. Apte M., Girme G., Bankar A., RaviKumar A., Zinjarde S. 3, 4-dihydroxy-L-phenylalanine-derived melanin from Yarrowia lipolytica mediates the synthesis of silver and gold nanostructures. J. Nanobiotechnology , 2013, vol. 11, no. 2, pp. 1-9.

14. Yuzhakov V.V., Kvetnoy I.M., Kuznetsova M.N., Havinson V.X., Fomina N.K. Kinetika rosta I fynkcionalnaya morfologia sarkomi M-1 y intaktnih kris posle gamma-oblycheniya [The kinetics and growth morphology functional sarcoma M-1 in intact rats after gamma-irradiation]. Voprosy onkologii – Questions of Oncology , 2001, vol. 47, no. 3. pp. 328-334.

15. Urbah Ju.V. Statisticheskij analiz v biologicheskih i medicinskih issledovanijah [Statistical analysis in biological and medical research]. Moscow, Medicina, 1964. 415 p.

16. Himmelblau D. Analiz processov statisticheskimi metodami [Process Analysis by Statistical Methods]. Mos-cow, Mir, 1975. 297 p.

17. Hainfeld J., Slatkin D., Smilowitz H. The use of gold nanoparticles to enhance radiotherapy in mice. Phys. Med. Biol. , 2004, vol. 49, no. 18, pp. 309-315.

18. Chang M.Y., Shiau A.L., Chen Y.H., Chang C.J., Chen H.H., Wu C.L. Increased apoptotic potential and dose-enhancing effect of gold nanoparticles in combination with single-dose clinical electron beams on tumor-bearing mice. Cancer Sci. , 2008, vol. 99, no. 7, pp. 1479-1484.

19. Ceresa C., Bravin A., Cavaletti G., Pellei M., Santini C. The combined therapeutical effect of metal-based drugs and radiation therapy: the present status of research. Curr. Med. Chem. , 2014, vol. 21, no. 20, pp. 2237-2265.

20. McQuade C., Al Zaki A., Desai Y., Vido M., Sakhuja T., Cheng Z., Hickey R.J., Joh D., Park S.J., Kao G., Dorsey J.F., Tsourkas A.A. Multifunctional nanoplatform for imaging, radiotherapy, and the prediction of therapeutic response. Small, 2015, vol. 11, no. 7, pp. 834-843.

21. Khlebtsov N.G., Bogatyrev V.A., Dykmanov L.A., Khlebtsov B.N. Zolotie nanostryktyri s plazmonnim resonansom dlya biomedicinskih issledovanii [Gold nanostructures with a plasmon resonance for biomedical research]. Rossijskie nanotehnologii – Russian Nanotechnologies , 2007, vol. 2, no 3, pp. 69-86.

22. Simon T., Boca-Farcau S., Gabudean A.M., Baldek P., Astilean S.J. LED-activated methylene blue-loaded Pluronic-nanogold hybrids in vitro photodynamic therapy. Biophotonics , 2013, vol. 6, no. 11-12, pp. 950-953.

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