Enhanced OH radical generation by dual-frequency ultrasound with TiO2 nanoparticles: Its application to targeted sonodynamic therapy

Ninomiya, Kazuaki; Noda, Kyohei; Ogino, Chiaki; Kuroda, Shinya; Shimizu, Nobuaki

doi:10.1016/j.ultsonch.2013.05.005

Cited by 109 publications

(75 citation statements)

References 37 publications

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“…SDT has attracted more interest as a promising therapy for the directed treatment of AS due to its minimal undesirable damage to surrounding normal tissues [28] and its deep penetration depth in tissues [8,9]. Our group found that low-intensity ultrasound induces little damage to tissue compared with high-intensity ultrasound [18,19,29].…”

Section: Discussionmentioning

confidence: 95%

Apoptosis of THP-1 Macrophages Induced by Pseudohypericin-Mediated Sonodynamic Therapy Through the Mitochondria-Caspase Pathway

Zheng

Shao

et al. 2016

Cell Physiol Biochem

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Background/Aims: Pseudohypericin (P-HY) and its congener hypericin are the major hydroxylated phenanthroperylenediones present in Hypericum species. Our previous study indicated that hypericin was able to function as a sonosensitizer. The potential use of P-HY as a sonosensitizer for sonodynamic therapy (SDT) requires further exploration. Thus, this study aimed to investigate the effects of P-HY-SDT on THP-1 macrophages. Methods: THP-1 macrophages were incubated with P-HY, and cell viability was measured using a CCK-8 assay. Fluorescence microscopy assessed the intracellular reactive oxygen species (ROS), mitochondrial membrane potential (∆Ψm) and mitochondrial permeability transition pore (mPTP) opening. Apoptotic and necrotic cell levels were measured by the flow cytometry analysis. Western blots were employed to assay BAX, Cytochrome C expression and apoptosis-related proteins. Results: P-HY-SDT induced THP-1 macrophage apoptosis. The levels of ROS were significantly increased in the SDT group, resulting in both mPTP opening and ∆Ψm loss, which led to apoptosis. In addition, the translocation of BAX, release of Cytochrome C and the upregulated expression of apoptosis-related proteins after P-HY-SDT were observed, all of which were reversed by N-acetyl cysteine (NAC). Conclusion: P-HY-SDT induced THP-1 macrophage apoptosis through the mitochondria-caspase pathway via ROS generation, the translocation of BAX and the release of Cytochrome C to regulate the mPTP opening.

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Section: Discussionmentioning

confidence: 95%

Apoptosis of THP-1 Macrophages Induced by Pseudohypericin-Mediated Sonodynamic Therapy Through the Mitochondria-Caspase Pathway

Zheng

Shao

et al. 2016

Cell Physiol Biochem

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“…More recently, several studies [91] highlighted the possibility to activate ROS formation through ultrasound irradiation. In this case the ROS production may be triggered by several mechanisms [111], as also schematized in Fig. 4 TiO 2 particles provide additional nuclei that increase the formation of ultrasound-induced cavitation bubbles.…”

Section: G Canavese Et Almentioning

confidence: 94%

“…Indeed, inertial cavitation phenomenon strongly depends on ultrasonic frequency, pressure amplitude, and, if pulsed ultrasound is used, on pulse repetition frequency and the number of cycles in each pulse [201]. In this regard, dual frequency ultrasound irradiation has also been recently proposed [111].…”

Section: Expert Opinion and Future Perspectivementioning

confidence: 99%

Nanoparticle-assisted ultrasound: A special focus on sonodynamic therapy against cancer

Canavese

Ancona

Racca

et al. 2018

Chemical Engineering Journal

351

247

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• Ultrasound-based therapies are opening new horizons in the oncological field.• Innovative and promising solutions derive from different nanoparticles-assisted ultrasound treatments.• Sonodynamic therapy (SDT) emerged recently as a novel approach for cancer treatment.• Different and complex cell death mechanisms are involved in nanoparticles-assisted SDT.• Nanoparticles-assisted ultrasound is still at its infancy in clinics. A R T I C L E I N F O Keywords:Inertial cavitation Reactive oxygen species Sonoluminescence Sonodynamic Tumor Therapy Cytotoxicity A B S T R A C TAt present, ultrasound radiation is broadly employed in medicine for both diagnostic and therapeutic purposes at various frequencies and intensities. In this review article, we focus on therapeutically-active nanoparticles (NPs) when stimulated by ultrasound. We first introduce the different ultrasound-based therapies with special attention to the techniques involved in the oncological field, then we summarize the different NPs used, ranging from soft materials, like liposomes or micro/nano-bubbles, to metal and metal oxide NPs. We therefore focus on the sonodynamic therapy and on the possible working mechanisms under debate of NPs-assisted sonodynamic treatments. We support the idea that various, complex and synergistics physical-chemical processes take place during acoustic cavitation and NP activation. Different mechanisms are therefore responsible for the final cancer cell death and strongly depends not only on the type and structure of NPs or nanocarriers, but also on the way they interact with the ultrasonic pressure waves. We conclude with a brief overview of the clinical applications of the various ultrasound therapies and the related use of NPs-assisted ultrasound in clinics, showing that this very innovative and promising approach is however still at its infancy in the clinical cancer treatment.

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“…Fortunately, an alternative therapy exists: low-intensity ultrasound can penetrate deeply into tissues due to its much lower attenuation coefficient in tissues compared with lasers. [7][8][9][10][11] To resolve the problem of penetration depth, we made use of low-intensity ultrasound as a substitute for light in this study.…”

Section: Introductionmentioning

confidence: 99%

The efficacy and mechanism of apoptosis induction by hypericin-mediated sonodynamic therapy in THP-1 macrophages

Li¹,

Gao²,

Zheng³

et al. 2015

IJN

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Purpose To investigate the sonoactivity of hypericin (HY), together with its sonodynamic effect on THP-1 macrophages and the underlying mechanism. Materials and methods CCK-8 was used to examine cell viability. Confocal laser scanning microscopy was performed to assess the localization of HY in cells, reactive oxygen species (ROS) generation, and opening of the mitochondrial permeability transition pore (mPTP) after different treatments. Apoptosis was analyzed using Hoechst–propidium iodide and transmission electron microscopy. Mitochondrial membrane potential (ΔΨm) collapse was detected via fluorescence microscopy. Lipoprotein oxidation was determined in malondialdehyde (MDA) assays. Western blotting was conducted to determine the translocation of BAX and cytochrome C and the expression of apoptosis-related proteins. Results HY was sublocalized among the nuclei and the mitochondria, endoplasmic reticulum, Golgi apparatus, and lysosome in the cytosol of THP-1 macrophages. Under low-intensity ultrasound irradiation, HY significantly decreased cell viability and induced apoptosis. Furthermore, greater ROS generation, higher MDA levels, and greater ΔΨm loss were observed in the sonodynamic therapy (SDT) group. Both ROS generation and MDA levels were significantly reduced by the ROS scavenger N-acetyl cysteine (NAC) and the singlet oxygen scavenger sodium azide. Most of the loss of ΔΨm was inhibited by pretreatment with NAC, sodium azide, and the mPTP inhibitor cyclosporin A (CsA). mPTP opening was induced upon SDT but was reduced by pretreatment with bongkrekic acid, 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid disodium, CsA, and NAC. Western blot analyses revealed translocation of BAX and cytochrome C, downregulated expression of Bcl-2, and upregulated expression of cleaved caspase-9, cleaved caspase-3, and cleaved poly(ADP-ribose) polymerase in the SDT group, which were reversed by NAC. Conclusion HY mediated SDT-induced apoptosis in THP-1 macrophages via ROS generation. Then, the proapoptotic factor BAX translocated from the cytosol to the mitochondria, increasing the ratio of BAX/Bcl-2, and the mPTP opened to release cytochrome C. This study demonstrated the great potential of HY-mediated SDT for treating atherosclerosis.

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Enhanced OH radical generation by dual-frequency ultrasound with TiO2 nanoparticles: Its application to targeted sonodynamic therapy

Cited by 109 publications

References 37 publications

Apoptosis of THP-1 Macrophages Induced by Pseudohypericin-Mediated Sonodynamic Therapy Through the Mitochondria-Caspase Pathway

Apoptosis of THP-1 Macrophages Induced by Pseudohypericin-Mediated Sonodynamic Therapy Through the Mitochondria-Caspase Pathway

Nanoparticle-assisted ultrasound: A special focus on sonodynamic therapy against cancer

The efficacy and mechanism of apoptosis induction by hypericin-mediated sonodynamic therapy in THP-1 macrophages

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