Endothelial Cells, First Target of Drug Delivery Using Microbubble-Assisted Ultrasound

Presset, Antoine; Bonneau, Corentin; Sasaoka, Kazuyoshi; Nadal-Desbarats, Lydie; Mitsuyoshi, Takigucho; Bouakaz, Ayache; Kudo, Nobuki; Escoffre, Jean‐Michel; Sasaki, Noboru

doi:10.1016/j.ultrasmedbio.2020.03.013

Cited by 28 publications

(24 citation statements)

References 111 publications

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“…Ultrasound exposure is known to increase cell membrane permeability and facilitate the delivery of drugs or genes into cells [ 18 , 19 ]. A combination of ultrasound exposure and microbubbles further increases cell membrane permeability even when using weak intensity ultrasound, leading to enhanced drug and gene uptake [ 12 , 13 , 14 , 15 , 16 , 17 ]. Stable oscillations of microbubbles are caused by exposure to low acoustic pressure, a process termed stable cavitation.…”

Section: Microbubbles and Nanobubblesmentioning

confidence: 99%

“…In recent years, nanoscale contrast agents have been developed. Furthermore, micro- or nanobubbles have previously been investigated as site-specific drug or gene delivery tools [ 12 , 13 , 14 , 15 , 16 , 17 ]. To exploit the combination of ultrasound and bubbles both for diagnosis and therapeutics as a theranostic system, various types of bubbles valuable for systemic administration have been well documented in recent years.…”

Section: Introductionmentioning

confidence: 99%

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Microbubbles and Nanobubbles with Ultrasound for Systemic Gene Delivery

Endo‐Takahashi

Negishi

2020

Pharmaceutics

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The regulation of gene expression is a promising therapeutic approach for many intractable diseases. However, its use in clinical applications requires the efficient delivery of nucleic acids to target tissues, which is a major challenge. Recently, various delivery systems employing physical energy, such as ultrasound, magnetic force, electric force, and light, have been developed. Ultrasound-mediated delivery has particularly attracted interest due to its safety and low costs. Its delivery effects are also enhanced when combined with microbubbles or nanobubbles that entrap an ultrasound contrast gas. Furthermore, ultrasound-mediated nucleic acid delivery could be performed only in ultrasound exposed areas. In this review, we summarize the ultrasound-mediated nucleic acid systemic delivery system, using microbubbles or nanobubbles, and discuss its possibilities as a therapeutic tool.

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Section: Microbubbles and Nanobubblesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Microbubbles and Nanobubbles with Ultrasound for Systemic Gene Delivery

Endo‐Takahashi

Negishi

2020

Pharmaceutics

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“…Microbubbles used for this application often contain a high molecular weight perfluorocarbon gas core surrounded by a protective shell made from lipids, proteins or polymers which improve their stability and lifetime [86]. The microbubbles can be co-administered intravenously along with drugs or other cargo, or can be designed to carry the therapeutic cargo inside the bubble or bound to the microbubble surface [87].…”

Section: Introduction To Ultrasound-microbubble Mediated Therapymentioning

confidence: 99%

Ultrasound and Microbubbles for Targeted Drug Delivery to the Lung Endothelium in ARDS: Cellular Mechanisms and Therapeutic Opportunities

et al. 2021

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Acute respiratory distress syndrome (ARDS) is characterized by increased permeability of the alveolar–capillary membrane, a thin barrier composed of adjacent monolayers of alveolar epithelial and lung microvascular endothelial cells. This results in pulmonary edema and severe hypoxemia and is a common cause of death after both viral (e.g., SARS-CoV-2) and bacterial pneumonia. The involvement of the lung in ARDS is notoriously heterogeneous, with consolidated and edematous lung abutting aerated, less injured regions. This makes treatment difficult, as most therapeutic approaches preferentially affect the normal lung regions or are distributed indiscriminately to other organs. In this review, we describe the use of thoracic ultrasound and microbubbles (USMB) to deliver therapeutic cargo (drugs, genes) preferentially to severely injured areas of the lung and in particular to the lung endothelium. While USMB has been explored in other organs, it has been under-appreciated in the treatment of lung injury since ultrasound energy is scattered by air. However, this limitation can be harnessed to direct therapy specifically to severely injured lungs. We explore the cellular mechanisms governing USMB and describe various permutations of cargo administration. Lastly, we discuss both the challenges and potential opportunities presented by USMB in the lung as a tool for both therapy and research.

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“…Microbubbles consist of a lipid, polymer, or protein shell and a gas core. Ultrasound stimulates the microbubbles to oscillate at their resonance frequency, damaging the adjacent endothelial cells and disrupting the tumor's vascular supply and leading to ischemia and necrosis of neoplastic cells [14,15]. Because tumor vasculature is disorganized and tortuous, the blood flow is slower, leading to longer exposure of the tumor endothelium to the microbubbles compared to the surrounding healthy vasculature.…”

Section: Introductionmentioning

confidence: 99%

Subsequent Ultrasound Vascular Targeting Therapy of Hepatocellular Carcinoma Improves the Treatment Efficacy

Sultan

Karmacharya

Hunt

et al. 2021

Biology

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The response of hepatocellular carcinoma (HCC) to anti-vascular ultrasound therapy (AVUS) can be affected by the inherent differences in tumor vascular structure, and the functionality of tumor vessels at the time of treatment. In this study, we evaluate the hypothesis that repeated subsequent AVUS therapies are a possible approach to overcome these factors and improve the therapeutic efficacy of AVUS. HCC was induced in 30 Wistar rats by oral ingestion of diethylnitrosamine (DEN) for 12 weeks. A total of 24 rats received treatment with low intensity, 2.8 MHz ultrasound with an intravenous injection of microbubbles. Treated rats were divided into three groups: single therapy group (ST), 2-days subsequent therapy group (2DST), and 7-days subsequent therapy group (7DST). A sham control group did not receive ultrasound therapy. Tumor perfusion was measured by quantitative contrast-enhanced ultrasound (CEUS) nonlinear and power-Doppler imaging. Tumors were harvested for histologic evaluation of ultrasound-induced vascular changes. ANOVA was used to compare the percent change of perfusion parameters between the four treatment arms. HCC tumors treated with 2DST showed the largest reduction in tumor perfusion, with 75.3% reduction on average for all perfusion parameters. The ST group showed an average decrease in perfusion of 54.3%. The difference between the two groups was significant p < 0.001. The 7DST group showed a reduction in tumor perfusion of 45.3%, which was significant compared to the 2DST group (p < 0.001) but not different from the ST group (p = 0.2). The use of subsequent targeted AVUS therapies applied shortly (two days) after the first treatment enhanced the anti-vascular effect of ultrasound. This gain, however, was lost for a longer interval (1 week) between the therapies, possibly due to tumor necrosis and loss of tumor viability. These findings suggest that complex interplay between neovascularization and tumor viability plays a critical role in treatment and, therefore, must be actively monitored following treatment by CEUS for optimizing sequential treatment.

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Endothelial Cells, First Target of Drug Delivery Using Microbubble-Assisted Ultrasound

Cited by 28 publications

References 111 publications

Microbubbles and Nanobubbles with Ultrasound for Systemic Gene Delivery

Microbubbles and Nanobubbles with Ultrasound for Systemic Gene Delivery

Ultrasound and Microbubbles for Targeted Drug Delivery to the Lung Endothelium in ARDS: Cellular Mechanisms and Therapeutic Opportunities

Subsequent Ultrasound Vascular Targeting Therapy of Hepatocellular Carcinoma Improves the Treatment Efficacy

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