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Exploring Different Ultrasonic Parameters and Treatment Conditions to Optimize In Vitro Sonodynamic Therapeutic Effects in Cancer Cells

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Abstract

The effects of ultrasonic parameters and treatment conditions on the in vitro cellular experiments of sonodynamic therapy (SDT) have not been fully studied. Exploring the factors that affect the efficacy of SDT can provide a reference for screening effective sonosensitizers in vitro. The aim of this work is to investigate the factors that affected the SDT effects in cancer cells. Cancer cells in culture plates were exposed to ultrasound and sonosensitizers. The intracellular drug concentration was measured by using flow cytometry and the cell viability was determined by MTT assay. The SDT effects of cancer cells treated with different ultrasonic parameters under the same sonosensitizer concentration were different. The ultrasonic parameters, intracellular drug concentration, drug treatment time, cell amount, and cell status could affect the sonodynamic therapeutic effects. It is necessary to select appropriate ultrasound conditions and optimize the cellular status to make the results of the in vitro cellular experiments more reliable.

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References

  1. Xu, J., Xia, X., Wang, X., Xu, C., Wang, P., Xiang, J., et al. (2010). Sonodynamic action of pyropheophorbide—A methyl ester in liver cancer cells. Journal of Ultrasound in Medicine, 29(7), 1031–1037

    Article  PubMed  Google Scholar 

  2. Suehiro, S., Ohnishi, T., Yamashita, D., Kohno, S., Inoue, A., Nishikawa, M., et al. (2018). Enhancement of antitumor activity by using 5-ALA-mediated sonodynamic therapy to induce apoptosis in malignant gliomas: Significance of high-intensity focused ultrasound on 5-ALA-SDT in a mouse glioma model. Journal of Neurosurgery, 129(6), 1416–1428

    Article  CAS  PubMed  Google Scholar 

  3. Osaki, T., Uto, Y., Ishizuka, M., Tanaka, T., Yamanaka, N. & Kurahashi, T. et al.(2017). Artesunate enhances the cytotoxicity of 5-aminolevulinic acid-based sonodynamic therapy against mouse mammary tumor cells in vitro. Molecules, 22, 4

    Article  Google Scholar 

  4. Shen, J., Cao, S., Sun, X., Pan, B., Cao, J., Che, D., et al. (2018). Sinoporphyrin sodium-mediated sonodynamic therapy inhibits RIP3 expression and induces apoptosis in the H446 small cell lung cancer cell line. Cellular Physiology and Biochemistry, 51(6), 2938–2954

    Article  CAS  PubMed  Google Scholar 

  5. Rosenthal, I., Sostaric, J. Z., & Riesz, P. (2004). Sonodynamic therapy—A review of the synergistic effects of drugs and ultrasound. Ultrasonics Sonochemistry, 11(6), 349–363

    Article  CAS  PubMed  Google Scholar 

  6. Wan, G. Y., Liu, Y., Chen, B. W., Liu, Y. Y., Wang, Y. S., & Zhang, N. (2016). Recent advances of sonodynamic therapy in cancer treatment. Cancer Biology & Medicine, 13(3), 325–338

    Article  CAS  Google Scholar 

  7. Snehota, M., Vachutka, J., Ter Haar, G., Dolezal, L., & Kolarova, H. (2020). Therapeutic ultrasound experiments in vitro: Review of factors influencing outcomes and reproducibility. Ultrasonics, 107, 106167

    Article  PubMed  Google Scholar 

  8. Geng, C., Zhang, Y., Hidru, T. H., Zhi, L., Tao, M., Zou, L., et al. (2018). Sonodynamic therapy: A potential treatment for atherosclerosis. Life Sciences, 207, 304–313

    Article  CAS  PubMed  Google Scholar 

  9. Ninomiya, K., Noda, K., Ogino, C., Kuroda, S. I., & Shimizu, N. (2014). Enhanced OH radical generation by dual-frequency ultrasound with TiO2 nanoparticles: Its application to targeted sonodynamic therapy. Ultrasonics Sonochemistry, 21(1), 289–294

    Article  CAS  PubMed  Google Scholar 

  10. Secomski, W., Bilmin, K., Kujawska, T., Nowicki, A., Grieb, P., & Lewin, P. A. (2017). In vitro ultrasound experiments: Standing wave and multiple reflections influence on the outcome. Ultrasonics, 77, 203–213

    Article  PubMed  PubMed Central  Google Scholar 

  11. Miyoshi, N., Sostaric, J. Z., & Riesz, P. (2003). Correlation between sonochemistry of surfactant solutions and human leukemia cell killing by ultrasound and porphyrins. Free Radical Biology & Medicine, 34(6), 710–719

    Article  CAS  Google Scholar 

  12. Zhu, B., Liu, Q., Wang, Y., Wang, X., Wang, P., Zhang, L., et al. (2010). Comparison of accumulation, subcellular location, and sonodynamic cytotoxicity between hematoporphyrin and protoporphyrin IX in L1210 cells. Chemotherapy, 56(5), 403–410

    Article  CAS  PubMed  Google Scholar 

  13. Liu, Y., Bai, H., Wang, H., Wang, X., Liu, Q., Zhang, K., et al. (2019). Comparison of hypocrellin B-mediated sonodynamic responsiveness between sensitive and multidrug-resistant human gastric cancer cell lines. Journal of Medical Ultrasonics, 46(1), 15–26

    Article  PubMed  Google Scholar 

  14. Zhang, P., Ren, Z., Chen, Z., Zhu, J., Liang, J., Liao, R., et al. (2018). Iron oxide nanoparticles as nanocarriers to improve chlorin e6-based sonosensitivity in sonodynamic therapy. Drug Design, Development and Therapy, 12, 4207–4216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Chang, N., Qin, D., Wu, P., Xu, S., Wang, S., & Wan, M. (2019). IR780 loaded perfluorohexane nanodroplets for efficient sonodynamic effect induced by short-pulsed focused ultrasound. Ultrasonics Sonochemistry, 53, 59–67

    Article  CAS  PubMed  Google Scholar 

  16. Prescott, M., Mitchell, J., Totti, S., Lee, J., Velliou, E., & Bussemaker, M. (2018). Sonodynamic therapy combined with novel anti-cancer agents, sanguinarine and ginger root extract: Synergistic increase in toxicity in the presence of PANC-1 cells in vitro. Ultrasonics Sonochemistry, 40(Pt B), 72–80

    Article  CAS  PubMed  Google Scholar 

  17. Varchi, G., Foglietta, F., Canaparo, R., Ballestri, M., Arena, F., Sotgiu, G., et al. (2015). Engineered porphyrin loaded core-shell nanoparticles for selective sonodynamic anticancer treatment. Nanomedicine, 10(23), 3483–3494

    Article  CAS  PubMed  Google Scholar 

  18. Osaki, T., Yokoe, I., Uto, Y., Ishizuka, M., Tanaka, T., Yamanaka, N., et al. (2016). Bleomycin enhances the efficacy of sonodynamic therapy using aluminum phthalocyanine disulfonate. Ultrasonics Sonochemistry, 28, 161–168

    Article  CAS  PubMed  Google Scholar 

  19. Chen, H. J., Zhou, X. B., Gao, Y., Zheng, B. Y., Tang, F. X., & Huang, J. D. (2014). Recent progress in development of new sonosensitizers for sonodynamic cancer therapy. Drug Discovery Today, 19(4), 502–509

    Article  CAS  PubMed  Google Scholar 

  20. Liu, Q., Li, X., Xiao, L., Wang, P., Wang, X., & Tang, W. (2008). Sonodynamically induced antitumor effect of hematoporphyrin on Hepatoma 22. Ultrasonics Sonochemistry, 15(6), 943–948

    Article  CAS  PubMed  Google Scholar 

  21. Yumita, N., Nishigaki, R., Umemura, K., & Umemura, S. I. (1989). Hematoporphyrin as a sensitizer of cell‐damaging effect of ultrasound. Japanese Journal of Cancer Research, 80(3), 219–222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Su, X., Wang, P., Wang, X., Guo, L., Li, S., & Liu, Q. (2013). Involvement of MAPK activation and ROS generation in human leukemia U937 cells undergoing apoptosis in response to sonodynamic therapy. International Journal of Radiation Biology, 89(11), 915–927

    Article  CAS  PubMed  Google Scholar 

  23. Zheng, R., Zhang, W., Wang, X., & Gao, H. (2010). The sonodynamic effects of Chlorin e6 on the proliferation of human lung adenocarcinoma cell SPCA-1. Zhongguo Fei Ai Za Zhi, 13(3), 201–205

    CAS  PubMed  Google Scholar 

  24. Kimura, T., Sakamoto, T., Leveque, J.-M., Sohmiya, H., Fujita, M., Ikeda, S., et al. (1996). Standardization of ultrasonic power for sonochemical reaction. Ultrasonics Sonochemistry 3(3), S157–S161

  25. O’Brien, W. D. (2007). Ultrasound—Biophysics mechanisms. Progress in Biophysics and Molecular Biology, 93(1–3), 212–255

    Article  PubMed  Google Scholar 

  26. Kasaai, M. R. (2013). Input power-mechanism relationship for ultrasonic irradiation food and polymer applications. Natural Science, 5(8), 14–22

    Article  Google Scholar 

  27. Barati, A. H., Mokhtari-Dizaji, M., Mozdarani, H., Bathaie, Z., & Hassan, Z. M. (2007). Effect of exposure parameters on cavitation induced by low-level dual-frequency ultrasound. Ultrasonics Sonochemistry, 14(6), 783–789

    Article  CAS  PubMed  Google Scholar 

  28. Kuroki, M., Hachimine, K., Abe, H., Shibaguchi, H., Kuroki, M., Maekawa, S.-I, et al. (2007). Sonodynamic therapy of cancer using novel sonosensitizers. Anticancer Research, 27(6A), 3673–3678

    CAS  PubMed  Google Scholar 

  29. Ter Haar, G. (2011). Ultrasonic imaging: Safety considerations. Interface Focus, 1(4), 686–697

    Article  PubMed  PubMed Central  Google Scholar 

  30. Lin, X. H., Song, J. B., Chen, X. Y., & Yang, H. H. (2020). Ultrasound activated sensitizers and applications. Angewandte Chemie International Edition, 59, 2–24

    Article  Google Scholar 

  31. Wang, P., Wang, X. B., Liu, Q. H., Tang, W., & Li, T. (2008). Enhancement of ultrasonically induced cytotoxic effect by hematoporphyrin in vitro. Chemotherapy, 54(5), 364–371

    Article  CAS  PubMed  Google Scholar 

  32. Hensel, K., Mienkina, M. P., & Schmitz, G. (2011). Analysis of ultrasound fields in cell culture wells for in vitro ultrasound therapy experiments. Ultrasound in Medicine and Biology, 37(12), 2105–2115

    Article  PubMed  Google Scholar 

  33. Poltawski, L., & Watson, T. (2007). Relative transmissivity of ultrasound coupling agents commonly used by therapists in the UK. Ultrasound in Medicine and Biology, 33(1), 120–128

    Article  PubMed  Google Scholar 

  34. Thanh Nguyen, T., Asakura, Y., Koda, S., & Yasuda, K. (2017). Dependence of cavitation, chemical effect, and mechanical effect thresholds on ultrasonic frequency. Ultrasonics Sonochemistry, 39, 301–306

    Article  PubMed  Google Scholar 

  35. Armour, E. P., & Corry, P. M. (1982). Cytotoxic effects of ultrasound in vitro dependence on gas content, frequency, radical scavengers, and attachment. Radiation Research, 89(2), 369–380

    Article  ADS  CAS  PubMed  Google Scholar 

  36. Pang, X., Xu, C. S., Jiang, Y., Xiao, Q. C., & Leung, A. W. (2016). Natural products in the discovery of novel sonosensitizers. Pharmacology & Therapeutics, 162, 144–151

    Article  CAS  Google Scholar 

  37. Sugita, N., Kawabata, K., Sasaki, K., Sakata, I., & Umemura, S. (2007). Synthesis of amphiphilic derivatives of rose bengal and their tumor accumulation. Bioconjugate Chemistry, 18(3), 866–873

    Article  CAS  PubMed  Google Scholar 

  38. Yumita, N., & Umemura, S. (2003). Sonodynamic therapy with photofrin II on AH130 solid tumor. Pharmacokinetics, tissue distribution and sonodynamic antitumoral efficacy of photofrin II. Cancer Chemotherapy and Pharmacology, 51(2), 174–178

    Article  CAS  PubMed  Google Scholar 

  39. Yumita, N., Nishigaki, R., & Umemura, S. (2000). Sonodynamically induced antitumor effect of Photofrin II on colon 26 carcinoma. Journal of Cancer Research and Clinical Oncology, 126(10), 601–606

    Article  CAS  PubMed  Google Scholar 

  40. Redmond, R. W., & Kochevar, I. E. (2006). Spatially resolved cellular responses to singlet oxygen. Photochemistry and Photobiology, 82(5), 1178–1186

    Article  CAS  PubMed  Google Scholar 

  41. Ozben, T. (2007). Oxidative stress and apoptosis: Impact on cancer therapy. Journal of Pharmaceutical Sciences, 96(9), 2181–2196

    Article  CAS  PubMed  Google Scholar 

  42. Kim, Y. S., Rhim, H., Choi, M. J., Lim, H. K., & Choi, D. (2008). High-intensity focused ultrasound therapy: An overview for radiologists. Korean Journal of Radiology, 9(4), 291–302

    Article  PubMed  PubMed Central  Google Scholar 

  43. VanBavel, E. (2007). Effects of shear stress on endothelial cells: Possible relevance for ultrasound applications. Progress in Biophysics and Molecular Biology, 93(1–3), 374–383

    Article  CAS  PubMed  Google Scholar 

  44. Lajoinie, G., De Cock, I., Coussios, C. C., Lentacker, I., Le Gac, S., Stride, E., et al. (2016). In vitro methods to study bubble-cell interactions: Fundamentals and therapeutic applications. Biomicrofluidics, 10(1), 011501

    Article  PubMed  PubMed Central  Google Scholar 

  45. Guzman, H. R., McNamara, A. J., Nguyen, D. X., & Prausnitz, M. R. (2003). Bioeffects caused by changes in acoustic cavitation bubble density and cell concentration: A unified explanation based on cell-to-bubble ratio and blast radius. Ultrasound in Medicine and Biology, 29(8), 1211–1222

    Article  PubMed  Google Scholar 

  46. Brayman, A. A., Church, C. C., & Miller, M. W. (1996). Re-evaluation of the concept that high cell concentrations “protect” cells in vitro from ultrasonically induced lysis. Ultrasound in Medicine and Biology, 22(4), 497–514

    Article  CAS  PubMed  Google Scholar 

  47. Shankar, H., & Pagel, P. S. (2011). Potential adverse ultrasound-related biological effects: A critical review. Anesthesiology, 115(5), 1109–1124

    Article  PubMed  Google Scholar 

  48. Sviridov, A. P., Andreev, V. G., Ivanova, E. M., Osminkina, L. A., Tamarov, K. P. & & Timoshenko, V. Y. (2013). Porous silicon nanoparticles as sensitizers for ultrasonic hyperthermia. Applied Physics Letters, 103, 19

    Article  Google Scholar 

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81871481 and 81571802), the Fujian Provincial Youth Top-notch Talent Support program, China and the Natural Science Foundation of Fujian Province (2022J01069).

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Authors and Affiliations

  1. Cancer Metastasis Alert and Prevention Center, and Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, College of Chemistry, Fuzhou University, Fuzhou, 350116, Fujian, China

    Yilin Zheng, Jun Wang & Yu Gao

  2. Key Laboratory of Molecule Synthesis and Function Discovery, College of Chemistry, Fuzhou University, Fuzhou, 350116, Fujian, China

    Haijun Chen

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  1. Yilin Zheng
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  2. Jun Wang
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  4. Yu Gao
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Y.Z.: writing—original draft, investigation, data curation. J.W.: investigation, validation. H.C.: resources. Y.G.: conceptualization, writing—review and editing, supervision, funding acquisition.

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Correspondence to Yu Gao.

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Zheng, Y., Wang, J., Chen, H. et al. Exploring Different Ultrasonic Parameters and Treatment Conditions to Optimize In Vitro Sonodynamic Therapeutic Effects in Cancer Cells. Cell Biochem Biophys 82, 303–314 (2024). https://doi.org/10.1007/s12013-023-01189-2

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