The Journal of the Acoustical Society of Korea (한국음향학회지)

The Acoustical Society of Korea (한국음향학회)
권호 표지
DOI QR코드

DOI QR Code

Sonoporation with echogenic liposome: therapeutic effect on a breast cancer cell

약물이 탑재된 미소기포와 결합된 sonoporation: 유방암세포에 대한 치료효과

  • Received : 2022.08.08
  • Accepted : 2022.09.06
  • Published : 2022.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Echogenic liposome contains both liquid and gas inside the shell. In ultrasound mediated drug delivery, sonoporation, these new microbubbles can be an attractive drug carrier since they can be loaded water soluble drugs and drug molecules can be unloaded at the specific location with ultrasound sonication. In this paper, the structure of the echogenic liposome was confirmed with EF-TEM and the positive effect of sonoporation with echogenic liposome was comparatively evaluated on MDA-MB-231 cells which is a type of breast cancer cell with Doxorubicin. Control group (Group 1), Doxorubicin only (Group 2), sonoporation with Doxorubicin and hollow microbubbles (Group 3), sonoporation with Doxorubicin loaded echogenic liposome (Group 4) were classified and experiments were conducted. According to the results, Group 4 is at least 1.4 times better in inducing necrosis of cancer cells. Therefore, we conclude echogenic liposome could be one of the most useful form of microbubbles in sonoporation.

공학적으로 제작된 미소기포 중 가스층과 유체층을 함께 내포하는 echogenic liposome은 수용성 약물 탑재에 용이하다. 또한 특정 위치에서 약물을 방출할 수 있다는 점에서 초음파 조영제의 기능을 넘어서 초음파 기반 약물전달(sonoporation)에 활용될 수 있다. 이에 따라, 본 논문에서는 이전 연구에서 제안된 echogenic liposome의 구조를 EF-TEM으로 재확인하였으며 sonoporation에서 약물전달 매개체로의 효과를 세포실험을 통하여 입증하였다. 세포실험은 유방암 조직인 MDA-MB-231 세포 대상으로 대표적 암치료제인 Doxorubicin을 지표 약물로 활용하였다. 비교군(1 그룹), Doxorubicin 그룹(2 그룹), Doxorubicin 과 일반 기포를 추가하여 sonoporation을 한 그룹(3 그룹), Doxorubicin을 echogenic liposome에 탑재하여 sonoporation을 적용한 그룹(4 그룹)으로 구분하여 진행한 실험결과, 4 그룹에서 약물 전달 효과가 초기부터 급격히 증가하였으며, 최종적으로 2 그룹과 3그룹에 비하여 최소 1.4 배 이상 효과적으로 종양 세포 괴사를 유도하였다. 따라서 sonoporation에서 echogenic liposome은 기존 일반적 미소기포보다 더 효율적인 약물 매개체라고 결론 내릴 수 있다.

Keywords

Acknowledgement

This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (2020R1A2C1008995).

References

  1. K. Ferrara, R. Pollard, and M. Borden, "Ultrasound microbubble contrast agents: fundamentals and application to gene and drug delivery," Annu. Rev. Biomed. Eng. 9, 415-447 (2007). https://doi.org/10.1146/annurev.bioeng.8.061505.095852
  2. P. A. Dayton and J. J. Rychak, "Molecular ultrasound imaging using microbubble contrast agents," Front. Biosci. 12, 5124-5142 (2007). https://doi.org/10.2741/2553
  3. K. E. Hitchcock, D. N. Caudell, J. T. Sutton, M. E. Klegerman, D. Vela, G. J. Pyne-Geithman, T. Abruzzo, P. E. P. Cyr, Y. J. Geng, D. D. McPherson, and C. K. Holland, "Ultrasound-enhanced delivery of targeted echogenic liposomes in a novel ex vivo mouse aorta model," J. Control. Release. 114, 288-295 (2010). https://doi.org/10.1016/j.jconrel.2006.06.008
  4. S. Hernot and A. L. Klibanov, "Microbubbles in ultrasound-triggered drug and gene delivery," Adv. Drug Deliv. Rev. 60, 1153-1166 (2008). https://doi.org/10.1016/j.addr.2008.03.005
  5. W. Lauterborn, T. Kurz, R. Geisler, D. Schanz, and O. Lindau, "Acoustic cavitation, bubble dynamics and sonoluminescence," Ultrason. Sonochem. 14, 484-491 (2007). https://doi.org/10.1016/j.ultsonch.2006.09.017
  6. R. E. Apfel, "Acoustic cavitation: a possible consequence of biomedical uses of ultrasound," Br. J. Cancer, 45, 140-146 (1982). https://doi.org/10.1038/bjc.1982.17
  7. P. A. Dijkmans, L. J. M. Juffermans, R. J. P. Musters, A van Wamel, F. J. ten Cate, W. van Gilst, C. A. Visser, N. de Jong, and O. Kamp, "Microbubbles and ultrasound: from diagnosis to therapy," Eur. J. Echocardiogr. 5, 245-256 (2004). https://doi.org/10.1016/j.euje.2004.02.001
  8. S. A. Elder, "Cavitation microstreaming," J. Acoust. Am. 31, 54-64 (1959). https://doi.org/10.1121/1.1907611
  9. K. B. Bader and C. K. Holland, "Gauging the likelihood of stable cavitation from ultrasound contrast agents," Phys. Med. Biol. 58, 127-144 (2013). https://doi.org/10.1088/0031-9155/58/1/127
  10. M. L. Fabiilli, K. J. Haworth, N. H. Fakhri, O. K. Kripfgans, P. L. Carson, and J. B. Fowlkes, "The role of inertial cavitation in acoustic droplet vaporization," IEEE Trans. Ultrason. Ferroelectr. Freq. Control. 56, 1006-1017 (2009). https://doi.org/10.1109/TUFFC.2009.1132
  11. L. Ye, X. Zhu, and X. Wei, "Ult rasonic cavit at ion damage characteristics of materials and a prediction model of cavitation impact load based on size effect," Int. J. Nanomed. 66, 105-115 (2020).
  12. D. Vancraeynest, X. Havaux, A. C. Pouleur, A. Pasquet, B. Gerber, C. Beauloye, P. Rafter, L. Bertrand, and J. L. J. Vanoverschelde, "Myocardial delivery of colloid nanoparticles using ultrasound targeted microbubble destruction," Eur. Heart J. 27, 237-245 (2006). https://doi.org/10.1093/eurheartj/ehi479
  13. H. Lee, H. Kim, H. Han, M. Lee, S. Lee, H. Yoo, J. H. Chang, and H. Kim, "Microbubbles used for contrast enhanced ultrasound and theragnosis: a review of principles to applications," Biomed. Eng. Lett. 7, 59-69 (2017). https://doi.org/10.1007/s13534-017-0016-5
  14. C. C. Coussions and R. A. Roy, "Applications of acoustics and cavitation to noninvasive therapy and drug delivery," Annu. Rev. Fluid Mech. 40, 395-420 (2008). https://doi.org/10.1146/annurev.fluid.40.111406.102116
  15. D. H. Park, H. C. Jung, J. Park, S. Bae, U. C. Shin, S. W. Kim, C. W. Kim, Y. H. Lee, and J. Seo, "Synthesis of echogenic liposomes for sonoporation," Micro & Nano Letters, 17, 276-285 (2022). https://doi.org/10.1049/mna2.12133
  16. J. Park, D. Park, U. Shin, S. Moon, C. Kim, H. S. Kim, H. Park, K. Choi, B. K. Jung, J. Oh, and J. Seo, "Synthesis of laboratory ultrasound contrast agents," Molecules, 18, 13078-13095 (2013). https://doi.org/10.3390/molecules181013078
  17. N. P. Ferreto and G. M. Calaf, "Influence of doxorubicin on apoptosis and oxidative stress in breast cancer cell lines," Int. J. Oncol. 49, 753-762 (2016). https://doi.org/10.3892/ijo.2016.3558
  18. I. Lentacker, B. Geers, J. Demeester, S. C De Smedt, and N. N Sanders, "Design and evaluation of doxorubicin-containing microbubbles for ultrasound-triggered doxorubicin delivery: cytotoxicity and mechanisms involved," Mol. Ther. 18, 101-108 (2010). https://doi.org/10.1038/mt.2009.160
  19. D. Sharma, K. X. Leong, and G. J. Czarnota, "Application of ultrasound combined with microbubbles for cancer therapy," Int. J. Mol. Sci. 23, 4393 (2022). https://doi.org/10.3390/ijms23084393
  20. D. Park, J. Park, H. Kim, C. H. Kim, T. Y. Han, H. Park, and J. Seo, "A high-precision angular control system for HIFU calibration," Ultrasonics, 53, 45-52 (2013). https://doi.org/10.1016/j.ultras.2012.03.012
  21. C. C. Church, "The effects of an elastic solid surface layer on the radial pulsations of gas bubbles," J. Acoust. Soc. Am. 97, 1510-1521 (1995). https://doi.org/10.1121/1.412091
  22. T. J. Leighton, The Acoustic Bubble (Academic Press, New York, 1994), pp 140-157.
  23. A. Kheirolomoom, P. A Dayton, A, F. H. Lum, E. Little, E. E. Paoli, H. Zheng, and K. W. Ferrar, "Acoustically-active microbubbles conjugated to liposomes: Characterization of a proposed drug delivery vehicle," J. Control. Release. 118, 275-284 (2007). https://doi.org/10.1016/j.jconrel.2006.12.015
  24. J. M. Escoffre, J. Piron, A. Novell, and A. Bouakaz, "Doxorubicin delivery into tumor cells with ultrasound and microbubbles," Mol. Pharm, 8, 799-806 (2011). https://doi.org/10.1021/mp100397p