RADIATION & RISK
Bulletin of the National Radiation and Epidemiological Registry
since 1992
About the Journal : 2015 : vol. 24, No. 3 : Assessment of cytotoxicity and tumor uptake of composites of hyaluronic acid and gold particles

Assessment of cytotoxicity and tumor uptake of composites of hyaluronic acid and gold particles

«Radiation and Risk», 2015, vol. 24, No. 3, pp.115-124

Authors

Koryakin S.N.1 – Lead. Researcher, C. Sc., Biol. A. Tsyb MRRC, Obninsk, Russia. Contacts: 4 Korolyov str., Obninsk, Kaluga region, Russia, 249036. Tel.: (484) 399-72-10; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. .
Ulianenko S.E.1 – Chief of Depart., D.Sc., Biol. A. Tsyb MRRC, Obninsk, Russia.
Isaeva E.V.1 – Senior Researcher, C. Sc., Biol. A. Tsyb MRRC, Obninsk, Russia.
Beketov E.E.1,2 – Senior Researcher, C. Sc., Biol. A. Tsyb MRRC, Obninsk, Russia. Institute for High Energy Physics (IHEP) of the National Research Centre of the Kurchatov Institute, Protvino, Russia.
Yadrovskaya V.A.1 – Lead. Researcher, C. Sc., Chem. A. Tsyb MRRC, Obninsk, Russia.
Uspenskiy S.A.3,4 – Lead. Researcher, C. Sc., Chem. Martinex Research Centre, Moscow, Russia. Enikolopov Institute of Synthetic Polymeric Materials, a foundation of the Russian Academy of Sciences, Moscow, Russia.
Selyanin M.A.3 – Gen. Director. Martinex Research Centre, Moscow, Russia.

Abstract

One of the ways to improve efficiency of radiation therapy is to use binary radiation therapy modalities, including photon capture therapy (PCT). Though PCT has a number of advantages: it is effective for treatment of radioresistant tumors, produces sparing effect on surrounding normal tissues, its further development depends to a large extent on availability of agents exhibiting high tumor uptake and low cytotoxicity. Composites of hyaluronic acid and gold particles are promising compounds for PCT. The article presents results of research into feasibility of using composites of melanin- modified hyaluronic acid salt and gold particles containing different amount of gold for photoncapture therapy. The in vivo study was carried out in B-16 melanoma – bearing male mice of F1 (CBAxC57Bl/6) strain, the in vitro study was carried out using B-16 melanoma cells culture. The composites with the gold content 1.5 or 2.2 mg in 0.1ml of solution were injected into the tumor in 12 days after the tumor cells inoculation. Gold uptake and excretion was measured during 3 hours following the injection. In 30 minutes gold uptake in the tumor was 17% of the total amount of the injected composite. We think that this is the most suitable time to deliver photon capture therapy. In in vitro studies minor effect of gold in concentration of 62.5 and 125 mcg in 1 ml of culture medium on inhibition of proliferation of B-16 melanoma cells was observed. Further study of the composites of melanin-modified hyaluronic acid salt and gold particles for improving efficiency of photoncapture therapy is needed.

Key words
Radiotherapy, target therapy, photon capture therapy, melanoma B-16, hyaluronic acid, melanin, gold containing complexes, nanocomposites, nanoparticles, ADME.

References

1. Gevorkov A.R., Bojko A.V., Zavalishina L.Je., Chernichenko A.V., Plavnik R.N., Hmelevskij E.V., Nosova E.A., Droshneva I.V., Smirnov A.K., Reshetov I.V., Rubcova N.A., Malysheva O.A., Sokolov V.V., Gladyshev A.A., Stepanov S.O., Solov'ev V.A. Samostojatel'noe konservativnoe i kombinirovannoe lechenie raka jazyka [Separate conservative and combined treatment of tongue cancer]. Onkologija. Zhurnal im. P.A. Gercena – Oncology. Journal of P.A. Gerzen, 2014, vol. 2, no. 4, pp. 25-29.

2. Kaprin A.D., Hmelevskij E.V., Semin A.V. Sochetannaja luchevaja terapija, kak al'ternativa hirurgicheskomu lecheniju pri mestnoraspolozhennom rake predstatel'noj zhelezy [Combined radiotherapy, as an alternative to surgical treatment of the local prostate cancer]. Vestnik Rossijskogo nauchnogo centra rentgenoradiologii Federal'nogo agentstva po vysokotehnologichnoj medicinskoj pomoshhi – Bulletin of the Russian Scientific Center of Radiology and the Federal Agency for High-tech Health Care, 2008, no. 6, pp. 22.

3. Hmelevskij E.V., Harchenko V.P., Pan'shin G.A., Mel'nik Ju.D., Ivanov S.A., Al'bickij I.A., Kancheli I.N., Klenok G.I., Lomanov M.F., Ljulevich V.I., Pohvata V.P., Rjazancev O.B., Horoshkov V.S. Metod protonno- fotonnoj luchevoj terapii lokalizovannogo raka predstatel'noj zhelezy [The method of proton-photon radiation therapy for localized prostate cancer]. Rossijskij onkologicheskij zhurnal – Russian Journal of Oncology, 2008, no. 6, pp. 13-16.

4. Choi G.-H., Seo S.-J., Kim K.-H., Kim H.-T., Park S.-H., Lim J.-H., Kim J.-K. Photon activated therapy (PAT) using monochromatic synchrotron X-rays and iron oxide nanoparticles in a mouse tumor model: feasibility study of PAT for the treatment of superficial malignancy. Radiation Oncology, 2012, vol. 184, no. 7, pp. 1-10.

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

6. 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.

7. 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.

8. Hainfeld J.J., Slatkin D.N., Smilowitz H.M. The use of gold nanoparticles to enhance radiotherapy in mice. Physics in Medicine and Biology, 2004. vol. 49, no. 18, pp. 309-315.

9. Rahman W.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.

10. 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. Journal of Nanobiotechnology, 2013, vol. 11, no. 2, pp. 1-9.

11. 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 activation therapies. Central European Journal of Biology, 2014, vol. 9, issue 10, pp. 922-930.

12. Urbah Ju.V. Statisticheskij analiz v biologicheskih i medicinskih issledovanijah [Statistical analysis in biological and medical research]. Moscow, Medicina, 1975. 297 p.

13. Jurlova E.I. Mehanizmy vlijanija T-kadgerina na rost, metastazirovanie i vaskuljarizaciju melanomy. Avtoref. diss. … kand. dis. biol. nauk [Mechanisms of influence of T-cadherin on the growth, metastasis and vascularization of melanoma. Kand. biology sci. diss.]. Moscow, 2011. 23 p.

14. Korman D.B. Osnovy protivoopuholevoj himioterapii [Fundamentals of anticancer chemotherapy]. Moscow, Prakticheskaja medicina, 2006. 503 p.

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