Sonodynamic therapy [Neurosurgery Wiki]

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====== Sonodynamic therapy ======
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{{rss>https://pubmed.ncbi.nlm.nih.gov/rss/search/1hAmdQvDK723TOHRZNx7dluk8EDtgaF6NYuHzQ3CIWH-NTP9qJ/?limit=15&utm_campaign=pubmed-2&fc=20250426100217}}
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Sonodynamic [[therapy]] is a type of [[cancer treatment]] that combines ultrasound waves with special compounds called sonosensitizers. These sonosensitizers accumulate more in tumor cells than in normal cells. When exposed to ultrasound, they produce reactive oxygen species (ROS) that can kill cancer cells, similar to how photodynamic therapy works with light instead of sound.

In short, sonodynamic therapy uses ultrasound plus a chemical agent to selectively destroy cancer cells.
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===== Effectiveness =====
The effectiveness of traditional inorganic semiconductor [[sonosensitizer]]s is hindered by rapid electron (e-) and hole (h+) recombination under ultrasonic (US) stimulation, as well as the hypoxic and reductive conditions of tumor microenvironment (TME), which limit the generation of reactive oxygen species (ROS). Herein, a ruthenium (Ru) single-atom nanozyme-driven superimposition-enhanced titanium dioxide-based sonosensitizer (Ru/TiO2-x SAE) is presented that features sufficient oxygen vacancies and high e-/h+ separation efficiency. Through synchrotron radiation-based X-ray absorption spectroscopy and extended X-ray absorption fine structure analysis, it is confirmed that oxygen vacancies in TiO2-x nanoparticles promote the immobilization of single-atomic Ru, forming Ru-O₄ active sites. Density functional theory calculations demonstrate that oxygen vacancies alter the electronic structure of the nanosensitizer, enhance e-/h+ separation, increase oxygen adsorption, and accelerate reaction kinetics under US stimulation, ultimately improving ROS production. Moreover, Ru/TiO2-x SAE boosts sonodynamic efficacy by mitigating the hypoxic and reductive TME. This is attributed to its catalase- and glutathione peroxidase 4-like activities, which facilitate the generation of ROS and trigger lipid peroxidation-mediated ferroptosis. These findings highlight the innovative role of single-atom Ru in optimizing sonosensitizers for SDT-induced ferroptosis, demonstrating its potential for advancing cancer therapy
((Zhu Y, Wang D, Du C, Wu T, Wei P, Zheng H, Li G, Zheng S, Su L, Yan L, Hu Y, Wang H, Lin L, Ding C, Chen X. [[Ruthenium]] Single-Atom Nanozyme Driven [[Sonosensitizer]] with Oxygen Vacancies Enhances Electron-Hole Separation Efficacy and Remodels [[Tumor Microenvironment]] for Sonodynamic-Amplified [[Ferroptosis]]. Adv Sci (Weinh). 2025 Apr 25:e2416997. doi: 10.1002/advs.202416997. Epub ahead of print. PMID: 40279631.)).
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Tserkovsky et al. is the first report to demonstrate the benefits of sono-photodynamic therapy (SPDT) consisting of low-power density ultrasound and PDT for the treatment of malignant glioma models
((Tserkovsky DA, Alexandrova EN, Chalau VN, Istomin YP. Effects of combined
sonodynamic and photodynamic therapies with photolon on a glioma C6 tumor model. 
Exp Oncol. 2012 Dec;34(4):332-5. PubMed PMID: 23302991.
)).
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Suehiro et al., from [[Matsuyama]] investigated the antitumor activity of [[sonodynamic therapy]] (SDT) combined with a sonosensitizer, [[5-aminolevulinic acid]] ([[5-ALA]]), on [[malignant glioma]]s to explore the possibility for clinical use of 5-ALA-mediated SDT (5-ALA-SDT). 

[[In vitro]] [[cytotoxicity]] of 5-ALA-SDT was evaluated in [[U87]] and [[U251]] [[glioma cell]]s and in U251Oct-3/4 glioma stemlike cells. Treatment-related [[apoptosis]] was analyzed using [[flow cytometry]] and TUNEL staining. Intracellular [[reactive oxygen species]] (ROS) were measured and the role of ROS in treatment-related cytotoxicity was examined by analysis of the effect of pretreatment with the radical scavenger [[edaravone]]. Effects of 5-ALA-SDT with [[high intensity focused ultrasound]] ([[HIFU]]) on tumor growth, survival of glioma-transplanted mice, and histological features of the mouse brains were investigated. 

The 5-ALA-SDT inhibited cell growth and changed cell morphology, inducing cell shrinkage, [[vacuolization]], and swelling. Flow cytometric analysis and TUNEL staining indicated that 5-ALA-SDT induced apoptotic cell death in all gliomas. The 5-ALA-SDT generated significantly higher ROS than in the control group, and inhibition of ROS generation by edaravone completely eliminated the cytotoxic effects of 5-ALA-SDT. In the in vivo study, 5-ALA-SDT with HIFU greatly prolonged survival of the tumor-bearing mice compared with that of the control group (p < 0.05). Histologically, 5-ALA-SDT produced mainly necrosis of the tumor tissue in the focus area and induced apoptosis of the tumor cells in the perifocus area around the target of the HIFU-irradiated field. The proliferative activity of the entire tumor was markedly decreased. Normal brain tissues around the ultrasonic irradiation field of HIFU remained intact.

The 5-ALA-SDT was cytotoxic toward malignant gliomas. Generation of ROS by the SDT was thought to promote apoptosis of [[glioma cell]]s. The 5-ALA-SDT with HIFU induced [[tumor necrosis]] in the focus area and apoptosis in the perifocus area of the HIFU-irradiated field, whereas the surrounding brain tissue remained normal, resulting in longer survival of the HIFU-treated mice compared with that of untreated mice. These results suggest that 5-ALA-SDT with HIFU may present a less invasive and tumor-specific therapy, not only for a tumor mass but also for infiltrating tumor cells in malignant gliomas
((Suehiro S, Ohnishi T, Yamashita D, Kohno S, Inoue A, Nishikawa M, Ohue S,
Tanaka J, Kunieda T. 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. J
Neurosurg. 2018 Jan 19:1-13. doi: 10.3171/2017.6.JNS162398. [Epub ahead of print]
PubMed PMID: 29350596.
)).

===2015===
Endo et al. investigated the efficacy of sonodynamic therapy of glioma cells in vitro using porphyrin derivatives, including 5-aminolevulinic acid, protoporphyrin IX and talaporfin sodium, as sonosensitizers. These substances have been known to accumulate in glioma cells and are expected to have cytotoxic effects on sonication. The study found that the cytotoxicity of sonication of glioma cells is enhanced by each sonosensitizer and that the efficacy of sonodynamic therapy may depend on the degree of intracellular accumulation of sonosensitizer. Also, the study suggests that induction of apoptosis is a major mechanism underlying cell death. Though further investigations are necessary, the preliminary result indicates a potential for sonodynamic therapy with sonosensitizers in glioma treatment
((Endo S, Kudo N, Yamaguchi S, Sumiyoshi K, Motegi H, Kobayashi H, Terasaka S,
Houkin K. Porphyrin Derivatives-Mediated Sonodynamic Therapy for Malignant
Gliomas In Vitro. Ultrasound Med Biol. 2015 Jun 10. pii: S0301-5629(15)00356-7.
doi: 10.1016/j.ultrasmedbio.2015.05.007. [Epub ahead of print] PubMed PMID:
26071619.
)).
===2014===

A study with a rat C6 glioma experimental model showed that SDT can potentially be useful in the treatment of deep-seated malignant gliomas
((Song D, Yue W, Li Z, Li J, Zhao J, Zhang N. Study of the mechanism of
sonodynamic therapy in a rat glioma model. Onco Targets Ther. 2014 Sep
30;7:1801-10. doi: 10.2147/OTT.S52426. eCollection 2014. PubMed PMID: 25336971;
PubMed Central PMCID: PMC4199795.
)).
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In vitro stimulation of calcium overload
and apoptosis by sonodynamic therapy combined with hematoporphyrin monomethyl
ether in C6 glioma cells((Dai S, Xu C, Tian Y, Cheng W, Li B. In vitro stimulation of calcium overload
and apoptosis by sonodynamic therapy combined with hematoporphyrin monomethyl
ether in C6 glioma cells. Oncol Lett. 2014 Oct;8(4):1675-1681. Epub 2014 Aug 5.
PubMed PMID: 25202390; PubMed Central PMCID: PMC4156202.))
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Calcium overload and in vitro apoptosis of the C6 glioma cells mediated by sonodynamic therapy (hematoporphyrin monomethyl ether and ultrasound)
((Hao D, Song Y, Che Z, Liu Q. Calcium overload and in vitro apoptosis of the C6
glioma cells mediated by sonodynamic therapy (hematoporphyrin monomethyl ether
and ultrasound). Cell Biochem Biophys. 2014 Nov;70(2):1445-52. doi:
10.1007/s12013-014-0081-7. PubMed PMID: 25158863; PubMed Central PMCID:
PMC4182584.
)).

===2008===
The data indicated that SDT could kill C6 glioma cells in vitro and possibility through induction of apoptosis and necrosis. Singlet oxygen ((1)O2) may play an important role in SDT
((Li JH, Song DY, Xu YG, Huang Z, Yue W. In vitro study of haematoporphyrin
monomethyl ether-mediated sonodynamic effects on C6 glioma cells. Neurol Sci.
2008 Sep;29(4):229-35. doi: 10.1007/s10072-008-0972-8. Epub 2008 Sep 20. PubMed
PMID: 18810596.
)).