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Sonodynamic Therapy on Intracranial Glioblastoma Xenografts Using Sinoporphyrin Sodium Delivered by Ultrasound with Microbubbles

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Abstract

Sonodynamic therapy (SDT) is a promising noninvasive method for cancer treatment. The anti-tumor effect of sinoporphyrin sodium (DVDMS)-mediated SDT on nude mice bearing intracranial U87 MG-Red-FLuc human glioblastoma was investigated. Focused ultrasound (FUS) with microbubbles (MBs) was utilized to open the blood-brain barrier for enhancing the delivery of the sonosensitizer DVDMS to the brain tumor first, and then the SDT treatment was performed. The in vitro study showed obvious cytotoxicity of DVDMS-mediated SDT (center frequency: 0.996 MHz, acoustic power: 1.7 W, pulse repletion frequency: 1 Hz, duty cycle: 30%, duration: 1 min) on U87 MG-Red-FLuc cells. The results indicated that more DVDMS accumulation in the tumor sites was induced by FUS with MBs by 3.43 folds of unsonicated ones. Longitudinal bioluminescence imaging illustrated that the intracranial glioblastoma progression in nude mice treated with SDT was retarded compared to the untreated group. The median survival time was prolonged to 30.25 days after SDT treatment by 27.37%. The anti-proliferation effect and cell apoptosis induction was further confirmed by immunohistochemical examinations. These results of the study suggested that SDT using the sonosensitizer DVDMS delivered by FUS with MBs may provide a new promising therapeutic strategy against glioblastoma.

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Acknowledgments

This work is supported by grants from the National Basic Research Program of China (Grant No. 2015CB755500), National Natural Science Foundation of China (Grant Nos. 81471735, 61427806, 81503215, 81501490), National Key Research and Development Program of China (Grant Nos. 2016YFC0104703, 2015BAI01B02), Medical Scientific Research Foundation of Guangdong Province (Grant No. A2017289), Project of Department of Education of Guangdong Province (Grant No. 2016KTSCX123), Province Natural Science Foundation of Guangdong (Grant No. 2015A030313593) and Shenzhen Science and Technology Planning Project (Grant Nos. JCYJ20160520175319943, JCYJ20150525092941057, JCYJ20160520175200003, JCYJ20160413164156155).

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Authors and Affiliations

  1. National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Xili Campus of Shenzhen University, 1066 Xueyuan Avenue, Shenzhen, 518071, People’s Republic of China

    Zhaoke Pi, Yongpeng Huang, Yuanyuan Shen, Yaxin Hu, Siping Chen & Xin Chen

  2. Shenzhen Second People’s Hospital, Shenzhen, People’s Republic of China

    Xiaojun Zeng

  3. Department of Pharmacy, Health Science Center, Shenzhen University, Shenzhen, People’s Republic of China

    Tie Chen & Chenyang Li

  4. Biomedical Engineering, Shenzhen Polytechnic, Shenzhen, People’s Republic of China

    Hao Yu

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  1. Zhaoke Pi
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  2. Yongpeng Huang
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Correspondence to Yuanyuan Shen or Xin Chen.

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Associate Editor Agata A. Exner oversaw the review of this article.

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10439_2018_2141_MOESM1_ESM.jpg

The fluorescence intensity of intracellular DVDMS accumulation in U87 MG-Red-FLuc cells with incubation time. Three wells were used for measurement at each time point. Supplementary material 1 (JPEG 288 kb)

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Pi, Z., Huang, Y., Shen, Y. et al. Sonodynamic Therapy on Intracranial Glioblastoma Xenografts Using Sinoporphyrin Sodium Delivered by Ultrasound with Microbubbles. Ann Biomed Eng 47, 549–562 (2019). https://doi.org/10.1007/s10439-018-02141-9

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  • DOI: https://doi.org/10.1007/s10439-018-02141-9

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