Disruption of Tumor Neovasculature by Microbubble Enhanced Ultrasound: A Potential New Physical Therapy of Anti-Angiogenesis

Liu, Zheng; Gao, Shunji; Yang, Zhao; Li, Peijing; Liu, Jia; Li, Peng; Tan, Kaibin; Xie, Feng

doi:10.1016/j.ultrasmedbio.2011.11.007

Cited by 75 publications

(93 citation statements)

References 23 publications

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“…In total, 18 experiments were designed, according to the L 18 (3) 6 orthogonal array, and the corresponding API values were obtained and listed in Table II. The values chosen for each level were based on the literature (10,15,16) and preliminary tests. In the 18 tests, various EUS perfusion changes were observed from the API quantification (Table II).…”

Section: Resultsmentioning

confidence: 99%

“…The anti-vascular effect of USMB is promising and reproducible (5,10,11,28). It has been demonstrated that thermal, mechanical, such as cavitation and other non-linear mechanisms, and sonochemical effects are likely to contribute to the anti-vascular activities of microbubbles (7).…”

Section: Discussionmentioning

confidence: 99%

“…The effects include increasing the vascular permeability for chemotherapy drugs and target gene delivery, opening the blood-brain barrier locally and transiently, and also vessel rupture and occlusion (9,10,13,21-25). Tumor blood perfusion may be blocked to various degrees using high-intensity focused US (HIFU) and low-frequency US (10,26,27). With the presence of microbubbles, this vascular disruption effect may be performed at a low acoustic intensity, and it overcomes the thermal adverse effects of HIFU ablation (15).…”

Section: Discussionmentioning

confidence: 99%

“…Since the survival and growth of solid tumors depends on tumor angiogenesis and physiological defects in the tumor neovasculature, there is considerable interest in developing techniques that target this neovasculature for cancer therapy. In addition to the numerous pharmacological agents that aim to inhibit or destroy tumor angiogenesis, in previous years there has been an increase in studies investigating a novel anti-vascular approach that uses low-frequency ultrasound and circulating microbubbles (USMB) to disrupt the tumor vasculature (8)(9)(10). This therapy has been confirmed to be capable of blocking off tumor blood perfusion without exhibiting an adverse impact on normal tissues.…”

Section: Introductionmentioning

confidence: 99%

“…Although there are certain studies that have investigated microbubble parameters, including size or shell properties or ultrasound pulse parameters, including the fundamental transmission frequency, pulse repetition frequency, duty cycle, pulse length, mechanical index and acoustic peak negative acoustic pressure (8,(10)(11)(12)(13), these studies investigated few parameters simultaneously and did not investigate the different combinations of various levels of parameters. In addition, these studies focused only on the therapeutic effects of USMB, and seldom considered the damage to the skin induced by USMB.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Optimization of low-frequency low-intensity ultrasound-mediated microvessel disruption on prostate cancer xenografts in nude mice using an orthogonal experimental design

Bai

Chen

et al. 2015

Oncology Letters

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Abstract. The present study aimed to provide a complete exploration of the effect of sound intensity, frequency, duty cycle, microbubble volume and irradiation time on low-frequency low-intensity ultrasound (US)-mediated microvessel disruption, and to identify an optimal combination of the five factors that maximize the blockage effect. An orthogonal experimental design approach was used. Enhanced US imaging and acoustic quantification were performed to assess tumor blood perfusion. In the confirmatory test, in addition to acoustic quantification, the specimens of the tumor were stained with hematoxylin and eosin and observed using light microscopy. The results revealed that sound intensity, frequency, duty cycle, microbubble volume and irradiation time had a significant effect on the average peak intensity (API). The extent of the impact of the variables on the API was in the following order: Sound intensity; frequency; duty cycle; microbubble volume; and irradiation time. The optimum conditions were found to be as follows: Sound intensity, 1.00 W/cm 2 ; frequency, 20 Hz; duty cycle, 40%; microbubble volume, 0.20 ml; and irradiation time, 3 min. In the confirmatory test, the API was 19.97±2.66 immediately subsequent to treatment, and histological examination revealed signs of tumor blood vessel injury in the optimum parameter combination group. In conclusion, the Taguchi L 18 (3) 6 orthogonal array design was successfully applied for determining the optimal parameter combination of API following treatment. Under the optimum orthogonal design condition, a minimum API of 19.97±2.66 subsequent to low-frequency and low-intensity mediated blood perfusion blockage was obtained.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Optimization of low-frequency low-intensity ultrasound-mediated microvessel disruption on prostate cancer xenografts in nude mice using an orthogonal experimental design

Bai

Chen

et al. 2015

Oncology Letters

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Selective depletion of tumor neovasculature by microbubble destruction with appropriate ultrasound pressure

Wang

Zhao

Shen

et al. 2015

Intl Journal of Cancer

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Low‐intensity ultrasound‐microbubble (LIUS‐MB) treatment is a promising antivascular therapy for tumors. We sought to determine whether LIUS‐MB treatment with an appropriate ultrasound pressure could achieve substantial and persistent cessation of tumor perfusion without having significant effects on normal tissue. Further, we investigated the mechanisms underlying this treatment. Murine S‐180 sarcomas, thigh muscles, and skin tissue from 60 tumor‐bearing mice were subjected to sham therapy, an ultrasound application combined with microbubbles in four different ultrasound pressures (0.5, 1.5, 3.0, 5.0 MPa), or ultrasound at 5.0 MPa alone. Subsequently, contrast‐enhanced ultrasonic imaging and histological studies were performed. Tumor microvessels, tumor cell necrosis, apoptosis, tumor growth, and survival were evaluated in 85 mice after treatment with the selected ultrasound pressure. We found that twenty‐four hours after LIUS‐MB treatment at 3.0 MPa, blood perfusion and microvessel density of the tumor had substantially decreased by 84 ± 8% and 84%, respectively (p < 0.01). Similar reductions were not observed in the muscle or skin. Additionally, an extreme reduction in the number of immature vessels was observed in the tumor (reduced by 90%, p < 0.01), while the decrease in mature vessels was not significant. Further, LIUS‐MB treatment at 3.0 MPa promoted tumor cell necrosis and apoptosis, delayed tumor growth, and increased the survival rate of tumor‐bearing mice (p < 0.01). These findings indicate that LIUS‐MB treatment with an appropriate ultrasound pressure could selectively and persistently reduce tumor perfusion by depleting the neovasculature. Therefore, LIUS‐MB treatment offers great promise for clinical applications in antivascular therapy for solid tumors.

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Oxygen‐sufficient lipid nanobubbles combined with UTMD for enhanced sonodynamic therapy of Hep‐G2 cells

et al. 2021

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Sonodynamic therapy (SDT) is an emerging noninvasive therapeutic approach, which could penetrate deep‐seated tissues and activate sonosensitizer to produce cytotoxic reactive oxygen species (ROS). Nevertheless, the hypoxic tumor microenvironment significantly limits the efficiency of SDT due to its oxygen‐consumption treatment principle. To break hypoxia‐induced resistance and improve the efficacy of SDT, we developed shell‐core structured oxygen‐sufficient nanobubbles(NBs), which were designed with a lipid shell loaded the sonosensitizer IR780 and a gas core loaded with oxygen. With the aid of ultrasound‐targeted microbubble destruction (UTMD), IR780@O2 NBs not only make sonosensitizers more effectively enriched at the tumor site in a controlled manner, but also directly mediate oxygen release and provide sufficient oxygen for producing more ROS to induce cell apoptosis. Thus, IR780@O2 NBs can efficiently inhibit the proliferation of Hep‐G2 cells under ultrasound exposure. What is more, IR780@O2 NBs have a potential for contrast enhanced ultrasound (CEUS) imaging. We believe that our oxygen‐sufficient NBs trigged by UTMD could be an ideal therapeutic and imaging system for hepatocellular carcinoma.

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Disruption of Tumor Neovasculature by Microbubble Enhanced Ultrasound: A Potential New Physical Therapy of Anti-Angiogenesis

Cited by 75 publications

References 23 publications

Optimization of low-frequency low-intensity ultrasound-mediated microvessel disruption on prostate cancer xenografts in nude mice using an orthogonal experimental design

Optimization of low-frequency low-intensity ultrasound-mediated microvessel disruption on prostate cancer xenografts in nude mice using an orthogonal experimental design

Selective depletion of tumor neovasculature by microbubble destruction with appropriate ultrasound pressure

Oxygen‐sufficient lipid nanobubbles combined with UTMD for enhanced sonodynamic therapy of Hep‐G2 cells

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