Introduction

Glioma remains incurable and a life limiting disease with an urgent need for effective therapies. Sonodynamic therapy (SDT) involves systemic delivery of non-toxic chemical agents (sonosensitizers) that accumulate in tumor cells or environment and are subsequently activated by exposure to low-frequency ultrasound to become cytotoxic agents. Herein, we discuss proposed mechanisms of action of SDT and provide recommendation for future research and clinical applications of SDT for gliomas.

Methods

Review of literature of SDT in glioma cell cultures and animal models published in Pubmed/MEDLINE before January, 2021.

Results

Different porphyrin and xanthene derivatives have proven to be effective sonosensitizers. Generation of reactive oxygen species and free radicals from water pyrolysis or sonosensitizers, or physical destabilization of cell membrane, have been identified as mechanisms of SDT leading to cell death. Numerous studies across glioma cell lines using various sonosensitizers and ultrasound parameters have documented tumoricidal effects of SDT. Studies in small animal glioma xenograft models have also consistently documented that SDT is associated with improved tumor control and longer survival of animals treated with SDT while avoiding damage of surrounding brain. There are no clinical trials completed to date regarding safety and efficacy of SDT in patients harboring gliomas, but some are beginning.

Conclusions

Pre-clinical studies cell cultures and animal models indicate that SDT is a promising treatment approach for gliomas. Further studies should define optimal sonication parameters and sonosensitizers for gliomas. Clinical trials of SDT in patients harboring gliomas and other malignant brain tumors are currently underway.

中文翻译：

---

神经胶质瘤的声动力疗法

介绍

神经胶质瘤仍然无法治愈，并且是一种限制生命的疾病，迫切需要有效的治疗方法。声动力疗法 (SDT) 涉及全身递送无毒化学剂（声敏剂），这些化学剂在肿瘤细胞或环境中积聚，随后通过暴露于低频超声而被激活，成为细胞毒性剂。在此，我们讨论了 SDT 的作用机制，并为 SDT 治疗胶质瘤的未来研究和临床应用提供建议。

方法

回顾 2021 年 1 月之前发表在 Pubmed/MEDLINE 上的胶质瘤细胞培养和动物模型中的 SDT 文献。

结果

不同的卟啉和呫吨衍生物已被证明是有效的声敏剂。水热解或声敏剂产生的活性氧和自由基，或细胞膜的物理不稳定，已被确定为 SDT 导致细胞死亡的机制。使用各种声敏剂和超声参数对神经胶质瘤细胞系进行的大量研究已经证明了 SDT 的杀肿瘤作用。对小动物胶质瘤异种移植模型的研究也一致证明，SDT 与改善肿瘤控制和延长接受 SDT 治疗的动物的存活率有关，同时避免损伤周围的大脑。迄今为止，尚无关于 SDT 在患有胶质瘤的患者中的安全性和有效性的临床试验完成，但一些试验已经开始。

结论

临床前研究细胞培养和动物模型表明，SDT 是一种很有前途的神经胶质瘤治疗方法。进一步的研究应确定胶质瘤的最佳超声参数和声敏剂。目前正在进行 SDT 在患有胶质瘤和其他恶性脑肿瘤的患者中的临床试验。