Chemistry, Physics and Technology of Surface, 2018, 9 (4), 353-361.

Synthesis and properties of magnetically sensitive nanocomposites based on magnetite and gemcitabine



DOI: https://doi.org/10.15407/hftp09.04.353

A. L. Petranovska, M. V. Abramov, N. M. Opanashchuk, S. P. Turanska, N. V. Kusyak, P. P. Gorbyk

Abstract


The aim of the work is synthesis of new polyfunctional magnetosensitive nanocomposites (NC) capable of the targeted delivery in the tumors of hepatocellular carcinoma and intrahepatic cholangiocarcinoma of a drug with chemotherapeutic mechanism of action – gemcitabine (GC), and deposition with the help of magnetic field, investigation of the basic physico-chemical properties of NC. Research direction includes synthesis of nanosized one-domain magnetite as a magnetically sensitive carrier, modification of its surface by carbon covering with the aim of stabilization and chemical functionalization, biofunctionalization of NC by GC immobilization.

For investigation the following samples of NC were synthesized: Fe3O4, Fe3O4/HА, Fe3O4/С. The choice of samples is explained by the necessity to obtain a protective biocompatible cover with high adsorptive properties on a surface of magnetosensitive carrier. Carbonization of Fe3O4 surface and obtaining of Fe3O4/С NC was realized with the help of an organic substance – CS polygel (Carbomer 934).

Adsorption of GC on a surface of magnetite and Fe3O4/HА, Fe3O4/С NC was carried out in aqueous medium in the concentration range С0 = 0.2–0.8 mg/L (g = 0.03 g, V = 5 mL, pH = 7.0) for 2 h in dynamic regime at room temperature. Amount of the adsorbed substance on a surface of NC was determined with the help of a spectrophotometer at λ = 268 nm from a calibration graph.

Adsorption characteristics were studied for surfaces of the synthesized NC with respect to GC. The results obtained show the dependence of adsorption capacity of the investigated samples on chemical nature of their surface. An increase in equilibrium GC concentration leads to a growth of adsorption capacity of Fe3O4/HА NC, which becomes almost in saturation for Fe3O4 and Fe3O4/С NC. The surfaces of NC researched are characterized by rather like values of adsorption parameters (А = 25–30 mg/g), which may be caused by similar nature of adsorption centers of their surfaces and adsorption mechanisms. GC extraction extent R (%) is 25–30 %.

Magnetic properties of NC with adsorbed gemcitabine Fe3O4/GC, Fe3O4/HА/GC, Fe3O4/С/GC were investigated with the help of a laboratory vibration magnetometer. An idea of the investigations is based on the use of an ensemble of superparamagnetic carriers as a probe for determination of parameters and control of core-shell type nanostructures with complex composition. Hysteresis loops were measured for magnetite particles, and NC with immobilized GC. It has been determined by the magnetic granulometry methods that the thickness of GC shell in the composition of Fe3O4/GC NC is (2.4±0.1) nm. Considering the thickness of GC layer is equal to 2.4 nm in all the studied nanostructures, we have found the value of thickness of hydroxyapatite layer in the structure of Fe3O4/HА/GC NC (3.5±0.1 nm), and the thickness of C layer in Fe3O4/С/GC NC (3.2±0.1 nm).

The obtained data may be useful in creation of medical magnetocarried nanosystems of targeted delivery and adsorptive materials for application in oncotherapy.


Keywords


gemcitabine; carbonization; hydroxyapatite; carbon coatings; surface; magnetite; magnetically sensitive nanocomposites; adsorption

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References


1. Shpak A.P., Gorbyk P.P. Physical chemistry of nanomaterials and supramolecular structures. (Kyiv: Naukova dumka, 2007). [in Russian].

2. Shpak A.P., Gorbyk P.P. Nanomaterials and Supramolecular Structures: Physics, Chemistry, and Applications. (Springer, 2009).

3. Gorbyk P.P., Petranovskaya A.L., Turelik M.P., Abramov N.V., Turanskaya S.P., Pilipchuk E.V., Chekhun V.F., Lukyanova N.Yu., Shpak A.P., Korduban A.M. Problem on directed drug transport: current status and prospects. Him. Fiz. Tehnol. Poverhni. 2011. 2(4): 433. [in Russian].

4. Gorbyk P.P., Turov V.V. Nanomaterials and Nanocomposites in Medicine, Biology, Ecology. (Kiev: Naukova Dumka, 2011). [in Russian].

5. Gorbyk P.P., Chekhun V.F. Nanocomposites of medicobiologic destination: reality and perspectives for oncology. Functional Materials. 2012. 19(2): 145.

6. Gorbyk P.P. Nanocomposites with functions of biomedical nanorobots: synthesis, properties, application. Nanosystems, nanomaterials, nanotechnologies. 2013. 11(2): 323. [in Ukrainian].

7. Uvarova I.V., Gorbyk P.P., Gorobets S.V., Ivashchenko O.A., Ulyanchenko N.V. Nanomaterials of Medical Purpose. (Kyiv: Naukova dumka, 2014). [in Ukrainian].

8. Gorbyk P.P., Lerman L.B., Petranovska A.L., Turanska S.P. Magnetosensitive nanocomposites with functions of medico-biological nanorobots: Synthesis and properties. Advances in Semiconductor Research: Physics of Nanosystems, Spintronics and Technological Applications. 2014. P. 161.

9. Gorbyk P.P., Lerman L.B., Petranovska A.L., Turanska S.P., Pylypchuk Ie.V. Magnetosensitive nanocomposites with hierarchical nanoarchitecture as biomedical nanorobots: synthesis, properties, and application. Fabrication and Self-Assembly of Nanobiomaterials, Applications of Nanobiomaterials. 2016. P. 289. https://doi.org/10.1016/B978-0-323-41533-0.00010-6

10. Abramov M.V., Kusyak A.P., Kaminskiy O.M., Turanska S.P., Petranovska A.L., Kusyak N.V., Gorbyk P.P. Magnetosensitive nanocomposites based on Cisplatin and Doxorubicin for application in oncology. Horizons in World Physics. 2017. 293: 1.

11. Patent UA 99211. Gorbyk P.P., Petanovskaya A.L., Turelik M.P., Korduban A.M., Shpak A.P., Chekhun V.F., Turanska S.P., Vasilieva O.A., Lukyanova N. Nanocapsule with functions of nanorobot. 2012.

12. Patent UA 78473 Paton B.E., Gorbyk P.P., Petranovskaya A.L., Turelik M.P., Abramov M.V., Vasilieva O.A., Chekhun V.F., Lukyanova N.Yu. Magnetic antitumor liquid. 2013.

13. Patent UA 112490 Chekhun V.F., Lukyanova N.Yu., Gorbyk P.P., Todor I.M., Petranovskaya A.L., Boshitskaya N.V., Bozhko I.V. Antitumor ferromagnetic nanocomposite. 2016.

14. Certificate 46056 Gorbyk P.P., Petanovskaya A.L., Turelik M.P., Abramov M.V., Vasilieva O.A. TTR (temporary technological regulation) on the for the production of the substance «Magnetite». 2012.

15. Certificate 58159 Gorbyk P.P., Abramov M.V., Petranovskaya A.L., Pylypchuk Ye.V., Vasilieva O.A. TTR (temporary technological regulations) for the production of magnetic liquid. 2015.

16. Antitumor nanocomposite «Feroplat». http://files.nas.gov.ua/NASDevelopmentsBook/PDF/0760.pdf.

17. Chekhun V.F. «Status and prospects for the implementation of nanotechnologies in biology and medicine. Ferroplat». http://iepor.org.ua/publications/feroplat.html.

18. Hepatocellular carcinoma (HCC): a global perspective.

19. Maystrenko O.N., Shaiko S.B., Alentiev A.V., Azimov F.Kh. Cholangiocellular cancer (features of diagnosis and treatment). Practical Oncology. 2008. 9(4): 229.

20. Kang T.W., Yevsa T., Woller N., Hoenicke L., Wuestefeld T., Dauch D., Hohmeyer A., Gereke M., Rudalska R., Potapova A., Iken M., Vucur M., Weiss S., Heikenwalder M., Khan S., Gil J., Bruder D., Manns M., Schirmacher P., Tacke F., Ott M., Luedde T., Longerich T., Kubicka S., Zender L. Senescence surveillance of pre-malignant hepatocytes limits liver cancer development. Nature. 2011. 479(7374): 547. https://doi.org/10.1038/nature10599

21. Yevsa T., Kang T.W., Zender L. Immune surveillance of pre-cancerous senescent hepatocytes limits hepatocellular carcinoma development. Oncoimmunology. 2012. 1(3): 398. https://doi.org/10.4161/onci.19128

22. Dauch D., Rudalska R., Cossa G., Nault J.C., Kang T.W., Wuestefeld T., Hohmeyer A., Imbeaud S., Yevsa T., Hoenicke L., Pantsar T., Bozko P., Malek N.P., Longerich T., Laufer S., Poso A., Zucman-Rossi J., Eilers M., Zender L. A MYC-aurora kinase A protein complex represents an actionable drug target in p53-altered liver cancer. Nat. Med. 2016. 22(7): 744. https://doi.org/10.1038/nm.4107

23. Plentz R.R., Malek N.P. Systemic Therapy of Cholangiocarcinoma. Visceral Medicine. 2016. 32(6): 427. https://doi.org/10.1159/000453084

24. Jain A., Kwong L.N., Javle M. Genomic Profiling of Biliary Tract Cancers and Implications for Clinical Practice. Curr. Treat. Options Oncol. 2016. 17(11): 58. https://doi.org/10.1007/s11864-016-0432-2

25. European pharmacopoeia. Art. Carbomers. 2001. P. 306.

26. Petranovska A.L., Abramov N.V., Turanska S.P., Gorbyk P.P., Kaminskiy A.N., Kusyak N.V. Adsorption of cis-dichlorodiammineplatinum by nanostructures based on single-domain magnetite. J. Nanostruct. Chem. 2015. 5(3): 275. https://doi.org/10.1007/s40097-015-0159-9

27. Abramov N.V., Turanska S.P., Kusyak A.P., Petranovska A.L., Gorbyk P.P. Synthesis and properties of magnetite/hydroxyapatite/doxorubicin nanocomposites and magnetic liquids based on them. J. Nanostruct. Chem. 2016. 6(3): 223. https://doi.org/10.1007/s40097-016-0196-z




DOI: https://doi.org/10.15407/hftp09.04.353

Copyright (©) 2018 A. L. Petranovska, M. V. Abramov, N. M. Opanashchuk, S. P. Turanska, N. V. Kusyak, P. P. Gorbyk

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