Focused tandem shock waves and their potential application in cancer treatment and controlled drug delivery
Project ID:GA202/09/1151
Provider:Czech Science Foundation
Period:Jan 01, 2009 - Dec 31, 2011
Recipient - coordinatorInstitute of Plasma Physics, Czech Academy of Sciences, Prague
Principal Investigator:Ing. Petr Lukeš, Ph.D.
Co-recepient(s) / PI(s):First Faculty of Medicine, Charles University in Prague -- Doc. MUDr. RND Jiří Beneš, CSc.
Faculty of Medicine and Dentistry, Palacky University -- Doc. RNDr. Hana Kolářová, CSc.
Co-investigators from IPPP. Šunka, P. Hoffer, V. Stelmashuk, V. Babický, J. Štraus

Aims of the project: The aim of the proposed project is to develop fundamental understanding of the mutual interaction of two successive shock waves focused to a common focal point - focused tandem shock waves (FTWS), their physical and chemical effects and their interactions with biological objects focused on the possible application of FTWS for cancer treatment and controlled drug delivery. For FTWS generation a novel type of generator will be used with ability to produce with adjustable delay two successive cylindrical pressure waves generated by underwater multichannel electrical discharge at a “composite” anode that are focused by a metallic parabolic reflector (cathode) and transformed into a strong shock wave. We expect that collapsing cavitations created by the second wave in evolution of cavitations produced by the first wave create secondary, short wavelength shocks that can be able to interact with cell scale structures. We suppose that by this way it could be possible to increase efficiency of chemotherapy treatment of cancers. These assumptions will be tested on cell suspensions, soft animal tissues, including cancer tissues and with liposomes and ex vivo and in vivo experiments on laboratory animals.

Progress/Results: New generator of focused two-successive (tandem) shock waves (FTSW) with fixed time delay between the waves of 10 µs was developed. Time delay between the waves at the focus is controlled by focal parameter of parabolic reflector and difference in diameter of composite discharge electrodes. Physical characteristics of FTSW generated in water (i.e., pressure amplitude, time and pressure profile of the shock at the focus) were described in dependence on the parameters of electrical discharge generated at porous ceramic-coated electrodes and on time delay between the waves. Dynamics of cavitation formed at the focus by interactions of the focused tandem shocks was described. A numerical model that provides analytical expressions for the temporal evolution of the pressure inside the cavitation bubbles and parameters of the pressure waveform of the second shock wave at the focal area was developed. It was demonstrated that cavitation play a key role in the physical effects induced by focused shock waves in water. It was shown that collapsing cavitation create secondary short wavelength shocks waves which interact with cell scale structures. Biological effects of FTSW were demonstrated in vitro on hemolysis of erythrocytes and on damage of cancer cells, chondrocytes, fibroplasts. It was proved in vivo that FTSW are capable of causing localized lesions at a predictable location deep within soft tissue at the focus without damaging tissue located in front of the focal point. It was demonstrated in vivo that FTSW can delay tumor growth and enhance antitumor effect of chemotherapeutic drugs such as cis-platinum or photosensitizer Photosan, possibly due to cavitation induced sonodynamic effect and increase permeability of membrane of cancer cells by FTSW.

Results:

Lukeš P., Šunka P., Hoffer P., Stelmashuk V., Poučková P., Zadinová M., Zeman J., Dibdiak L., Kolářová H., Tománková K., Binder S., Beneš J.: Focused tandem shock waves in water and their potential application in cancer treatment. Shock Waves 24 [1] (2014) 51-57. [ Abstract ] [ Link ]
[International Symposium on Shock Waves/28./. Manchester, 17.07.2011-22.07.2011]

Beneš J., Zeman J., Poučková P., Zadinová M., Šunka P., Lukeš P.: Biological effects of tandem shock waves demonstrated on magnetic resonance. Bratislavske Lekarske Listy 113 [6] (2012) 335-338. [ Abstract ] [ Link ]

Lukeš P., Šunka P., Hoffer P., Stelmashuk V., Beneš J., Poučková P., Zadinová M., Zeman J.: Generation of Focused Shock Waves in Water for Biomedical Applications. Plasma for Bio-Decontamination, Medicine and Food Security. Dordrecht : Springer, 2012 - (Machala, Z.; Hensel, K.; Akishev, Y.) s. 403-416. ISBN 978-94-007-2851-6 [ Abstract ] [ Link ]

Zeman J., Hach J., Dibdiak L., Šunka P., Lukeš P., Hoffer P., Sedláček R., Kociová K., Beneš J.: Účinek rázové vlny na kostní cement a její potenciální využití v ortopedii. Ortopedie 6 [3] (2012) 100-102. [ Abstract ] [ Link ]

Stelmashuk V., Lukeš P., Hoffer P.: Effect of solution conductivity on shock wave pressure generated by multichannel electrical discharge in water. 28th International Symposium on Shock Waves. Volume 2, Part XXI: Special Session Medical and Biological Applications. Berlin Heidelberg : Springer Verlag GmbH, 2012 - (Kontis, K.), s. 599-604 ISBN 978-3-642-25684-4 [ Abstract ] [ Link ]

Lukeš P., Šunka P., Hoffer P., Stelmashuk V., Beneš J., Poučková P., Zadinová M., Zeman J., Dibdiak L., Kolářová H., Tománková K., Binder S.: Focused tandem shock waves in water and their potential application in cancer treatment. 28th International Symposium on Shock Waves. Volume 2, Part XXI: Special Session Medical and Biological Applications. Berlin Heidelberg : Springer Verlag GmbH, 2012 - (Kontis, K.), s. 839-845 ISBN 978-3-642-25684-4 [ Abstract ] [ Link ]

Stelmashuk V., Lukeš P., Hoffer P.: Effect of solution conductivity on shock wave pressure generated by multichannel electrical discharge. Proceedings of 28th International Symposium on Shock Waves. Manchester : Springer Verlag, 2011. P-2698-P-2698. ISBN 978-3-642-25687-5. [ Abstract ]
[International Symposium on Shock Waves/28./. Manchester (GB), 17.07.2011-22.07.2011]

Lukeš P., Šunka P., Hoffer P., Stelmashuk V., Beneš J., Poučková P., Zeman J., Dibdiak L., Kolářová H., Tománková K., Binder S.: Focused tandem shock waves in water and their potential application in cancer treatment. Proceedings of 28th International Symposium on Shock Waves. Manchester : Springer Verlag, 2011. P-2849-P-2849. ISBN 978-3-642-25687-5. [ Abstract ]
[International Symposium on Shock Waves/28./. Manchester (GB), 17.07.2011-22.07.2011]

Hoffer P., Šunka P., Lukeš P.: Dynamics of cavitation induced by focused tandem shock waves in water. WDS'11 Proceedings of Contributed Papers: Part II: Physics of Plasmas and Ionized Media. Praha : MATFYZPRESS, 2011 - (Šafránková, J.; Pavlů, J.) s. 267-272. ISBN 978-80-7378-185-9. [ Abstract ]
[WDS 2011 - Annual Conference of Doctoral Students /20./. Prague (CZ), 31.05.2011-03.06.2011]

Hoffer P., Šunka P., Stelmashuk V.: Dynamics of cavitations induced by tandem shock waves in water. Proceedings of the XXIX International Conference on Phenomena in Ionized Gases. Cancun, Mexico : Institute of Physics (IOP)., 2009. PA4-5-8. ISBN N. - (ICPIG). [ Abstract ]
[International Conference on Phenomena in Ionized Gases 2009/29th./. Cancún (MX), 12.07.2009-17.07.2009]