Synergistic Efficacy of Ultrasound, Sonosensitizers and Chemotherapy: A Review

Hirschberg, Henry; Madsen, Steen J.

doi:10.4155/tde-2016-0080

Cited by 27 publications

(36 citation statements)

References 67 publications

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“…These data support the hypothesis that the possible mechanism of action for effective sonodynamic anticancer response derives from the ROS elicited by the US activation of the sensitiser, such as in the well-clinically established PDT technique where cancer cell killing is achieved through oxidative stress. We thus feel, as do other authors [60][61][62], that sonodynamic treatment deserves further investigation for its potential as an intriguing strategy for cancer treatment.…”

Section: Discussionsupporting

confidence: 51%

Insight into ultrasound-mediated reactive oxygen species generation by various metal-porphyrin complexes

Giuntini

Foglietta

Marucco

et al. 2018

Free Radical Biology and Medicine

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Ultrasound is used to trigger the cytotoxicity of chemical compounds, known as sonosensitisers, in an approach called sonodynamic therapy (SDT), which is under investigation herein. The generation of reactive oxygen species (ROS) has been proposed as the main biological occurrence that leads to the cytotoxic effects, which are achieved via the synergistic action of two components: the energy-absorbing sonosensitiser and ultrasound (US), which are both harmless per se. Despite some promising results, a lack of investigation into the mechanisms behind US sonosensitiser-mediated ROS generation has prevented SDT from reaching its full potential. The aim of this work is to investigate the US-responsiveness of a variety of metal-porphyrin complexes, free-base porphyrin and Fe(III), Zn(II) and Pd(II) porphyrin, by analyzing their ROS generation under US exposure and related bio-effects. All experiments were also carried out under light exposure and the results were used as references. Our results show that porphyrin ultrasound-responsiveness depends on the metal ion present, with Zn(II) and Pd(II) porphyrin being the most efficient in generating singlet oxygen and hydroxyl radicals. ROS production efficiency is lower after ultrasound exposure than after light exposure, because of the various physico-chemical mechanisms involved in sensitiser activation. US and porphyrin-mediated ROS generation is oxygen-dependent and the activation of porphyrin by US appears to be more compatible with sonoluminescence-based photo-activation rather than a radical path process that occurs via the homolytic bond rupture of water. Notably, the cytotoxicity results reported herein, which are mirrored by ex-cellulo data, confirm that the type of ROS generation achieved by the US activation of intracellular porphyrins is pivotal to the effectiveness of cancer cell killing.

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Section: Discussionsupporting

confidence: 51%

Insight into ultrasound-mediated reactive oxygen species generation by various metal-porphyrin complexes

Giuntini

Foglietta

Marucco

et al. 2018

Free Radical Biology and Medicine

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“…VLIUS has been utilized for cancer therapy studies - sonodynamic therapy, US mediated chemotherapy, US mediated gene delivery and antivascular US therapy [34]. Focused US has been used recently to target DNA-loaded microbubbles located within tumor’s neovasculature to facilitate release of genetic material locally into the tumor [35, 36]. In particular, US has been noted causing the process of sonoporation thus producing transient pores in the cancer cell membranes through which molecules are able to enter the cell [20, 37, 38].…”

Section: Discussionmentioning

confidence: 99%

Very low intensity ultrasounds as a new strategy to improve selective delivery of nanoparticles-complexes in cancer cells

Loria

Giliberti

Bedini

et al. 2019

J Exp Clin Cancer Res

343

233

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BackgroundThe possibility to combine Low Intensity UltraSound (LIUS) and Nanoparticles (NP) could represent a promising strategy for drugs delivery in tumors difficult to treat overcoming resistance to therapies. On one side the NP can carry drugs that specifically target the tumors on the other the LIUS can facilitate and direct the delivery to the tumor cells. In this study, we investigated whether Very Low Intensity UltraSound (VLIUS), at intensities lower than 120 mW/cm2, might constitute a novel strategy to improve delivery to tumor cells. Thus, in order to verify the efficacy of this novel modality in terms of increase selective uptake in tumoral cells and translate speedily in clinical practice, we investigated VLIUS in three different in vitro experimental tumor models and normal cells adopting three different therapeutic strategies.MethodsVLIUS at different intensities and exposure time were applied to tumor and normal cells to evaluate the efficiency in uptake of labeled human ferritin (HFt)-based NP, the delivery of NP complexed Firefly luciferase reported gene (lipoplex-LUC), and the tumor-killing of chemotherapeutic agent.ResultsSpecifically, we found that specific VLIUS intensity (120 mW/cm2) increases tumor cell uptake of HFt-based NPs at specific concentration (0.5 mg/ml). Similarly, VLIUS treatments increase significantly tumor cells delivery of lipoplex-LUC cargos. Furthermore, of interest, VLIUS increases tumor killing of chemotherapy drug trabectedin in a time dependent fashion. Noteworthy, VLIUS treatments are well tolerated in normal cells with not significant effects on cell survival, NPs delivery and drug-induced toxicity, suggesting a tumor specific fashion.ConclusionsOur data shed novel lights on the potential application of VLIUS for the design and development of novel therapeutic strategies aiming to efficiently deliver NP loaded cargos or anticancer drugs into more aggressive and unresponsive tumors niche.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-1018-6) contains supplementary material, which is available to authorized users.

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“…Therefore, it is necessary to increase the efficacy of HIFU. Many studies have confirmed that both microbubbles and SDT can improve the efficacy of HIFU [15, 16, 35]. The N 2 O-loaded microbubbles prepared in this study have a smaller particle size, but similar characteristics as ultrasonic microbubble contrast agents.…”

Section: Discussionmentioning

confidence: 59%

“…In addition, microbubbles as an exogenous cavitation nucleus also reduce the tissue cavitation threshold and enhance the cavitation effect of HIFU as it passes through the blood circulation into the tumor tissue [14]. In recent years, studies have indicated that sonodynamic therapy (SDT) can synergistically enhance HIFU treatment efficacy [15, 16]. The interactions between the sonosensitizers and ultrasound produce reactive oxygen species (ROS), including singlet oxygen and hydroxyl radicals, which kill tumor cells and inhibit tumor growth via apoptosis and necrosis [17].…”

Section: Introductionmentioning

confidence: 99%

The Study of Enhanced High-Intensity Focused Ultrasound Therapy by Sonodynamic N2O Microbubbles

et al. 2019

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High-intensity focused ultrasound (HIFU) is a representative non-invasive method of cancer therapy, but its low therapeutic efficacy and risk of damage to surrounding normal tissue hinder its further clinical development and application. Sonodynamic therapy (SDT) kills tumor cells through reactive oxygen molecules produced by sonosensitizers during ultrasound treatment. SDT can enhance HIFU efficacy like microbubbles. In this work, we developed nanoscale N2O microbubbles (N2O-mbs) by an improved mechanical oscillation method. These microbubbles showed good biocompatibility and tumor cell binding. The sonosensitivity of the N2O-mbs was detected both extracellularly and intracellularly through the detection of reactive oxygen species generation. The toxic effects of these sonodynamic microbubbles on tumor cells and the synergistic effect on HIFU treatment were evaluated. Significant apoptosis was caused by reactive oxygen species produced by N2O-mbs under ultrasound irradiation. N2O-mbs combined with HIFU increased tumor cell necrosis and apoptosis in vitro and the coagulative necrotic volume and echo intensity in the bovine liver target area ex vivo. These sonodynamic microbubbles have been also demonstrated to efficiently inhibit tumor growth in vivo. N2O-mbs have a significant impact on the treatment and ablation effect of HIFU due to the advantages of microbubble and extraordinary sonosensitivity. This finding suggests that N2O-mbs may be a novel auxiliary agent for ultrasound that can be used to promote HIFU tumor thermal ablation.

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Synergistic Efficacy of Ultrasound, Sonosensitizers and Chemotherapy: A Review

Cited by 27 publications

References 67 publications

Insight into ultrasound-mediated reactive oxygen species generation by various metal-porphyrin complexes

Insight into ultrasound-mediated reactive oxygen species generation by various metal-porphyrin complexes

Very low intensity ultrasounds as a new strategy to improve selective delivery of nanoparticles-complexes in cancer cells

The Study of Enhanced High-Intensity Focused Ultrasound Therapy by Sonodynamic N2O Microbubbles

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