Viability of endothelial cells after ultrasound-mediated sonoporation: Influence of targeting, oscillation, and displacement of microbubbles

Rooij, Tom van; Skachkov, Ilya; Beekers, Inés; Lattwein, Kirby R.; Voorneveld, Jason; Kokhuis, Tom J. A.; Bera, Debaditya; Luan, Ying; Steen, Antonius F.W. van der; Jong, Nico de; Kooiman, Klazina

doi:10.1016/j.jconrel.2016.07.037

Cited by 80 publications

(100 citation statements)

References 61 publications

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“…In this study, propidium iodide (PI; final concentration 30 μg/mL) was used to determine the damage to the cell membrane after ADV. Since PI is a live-cell impermeable model drug, it can only pass through a disrupted cell membrane to bind to DNA and RNA and become fluorescent 17, 43. In order to prevent the violent mechanical forces induced by ADV from blowing cells out of the optical view, 1×10 10 DiI-NDs were added to the cell dish for a 10 min incubation to obtain a ratio of one DiI-ND per 2-3 cells.…”

Section: Methodsmentioning

confidence: 99%

Theranostic Performance of Acoustic Nanodroplet Vaporization-Generated Bubbles in Tumor Intertissue

Ho¹,

Yeh²

2017

Theranostics

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Solid tumors with poorly perfused regions reveal some of the treatment limitations that restrict drug delivery and therapeutic efficacy. Acoustic droplet vaporization (ADV) has been applied to directly disrupt vessels and release nanodroplets, ADV-generated bubbles (ADV-Bs), and drugs into tumor tissue. In this study, we investigated the in vivo behavior of ADV-Bs stimulated by US, and evaluated the possibility of moving intertissue ADV-Bs into the poorly perfused regions of solid tumors. Intravital imaging revealed intertissue ADV-B formation, movement, and cavitation triggered by US, where the distance of intertissue ADV-B movement was 33-99 µm per pulse. When ADV-Bs were applied to tumor cells, the cell membrane was damaged, increasing cellular permeability or inducing cell death. The poorly perfused regions within solid tumors show enhancement due to ADV-B accumulation after application of US-triggered ADV-B. The intratumoral nanodroplet or ADV-B distribution around the poorly perfused regions with tumor necrosis or hypoxia were demonstrated by histological assessment. ADV-B formation, movement and cavitation could induce cell membrane damage by mechanical force providing a mechanism to overcome treatment limitations in poorly perfused regions of tumors.

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Section: Methodsmentioning

confidence: 99%

Theranostic Performance of Acoustic Nanodroplet Vaporization-Generated Bubbles in Tumor Intertissue

Ho¹,

Yeh²

2017

Theranostics

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“…Endothelial cell sonoporation with FUS and MBs has been explored extensively in vitro. These studies have demonstrated the formation of membrane pores on endothelial cells following MB oscillation-induced shear stress as well as the initiation of intercellular gaps between adjacent cells and induction of endocytosis, all of which could facilitate the delivery of therapeutic agents (36,(71)(72)(73)(74)(75)(76)(77)(78). The effects of acoustic sonoporation have been investigated in vivo as well (30,31,79), but to date no studies have utilized FUS to achieve targeted sonoporation of endothelial cells in vivo without disruption of tight junctions and/ or enhancement of transcellular transport that would allow for therapeutic delivery beyond the vasculature.…”

mentioning

confidence: 99%

Sonoselective transfection of cerebral vasculature without blood–brain barrier disruption

Gorick

Mathew

Garrison

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Treatment of many pathologies of the brain could be improved markedly by the development of noninvasive therapeutic approaches that elicit robust, endothelial cell-selective gene expression in specific brain regions that are targeted under MR image guidance. While focused ultrasound (FUS) in conjunction with gasfilled microbubbles (MBs) has emerged as a noninvasive modality for MR image-guided gene delivery to the brain, it has been used exclusively to transiently disrupt the blood-brain barrier (BBB), which may induce a sterile inflammation response. Here, we introduce an MR image-guided FUS method that elicits endothelialselective transfection of the cerebral vasculature (i.e., "sonoselective" transfection), without opening the BBB. We first determined that activating circulating, cationic plasmid-bearing MBs with pulsed low-pressure (0.1 MPa) 1.1-MHz FUS facilitates sonoselective gene delivery to the endothelium without MRI-detectable disruption of the BBB. The degree of endothelial selectivity varied inversely with the FUS pressure, with higher pressures (i.e., 0.3-MPa and 0.4-MPa FUS) consistently inducing BBB opening and extravascular transfection. Bulk RNA sequencing analyses revealed that the sonoselective low-pressure regimen does not up-regulate inflammatory or immune responses. Single-cell RNA sequencing indicated that the transcriptome of sonoselectively transfected brain endothelium was unaffected by the treatment. The approach developed here permits targeted gene delivery to blood vessels and could be used to promote angiogenesis, release endothelial cellsecreted factors to stimulate nerve regrowth, or recruit neural stem cells.focused ultrasound | microbubbles | endothelium | gene delivery

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“…In particular, using human [umbilical vein] endothelial cell (HUVEC) monolayer cultures (Helfield et al 2016), it was found that ultrasound/microbubble-mediated sonoporation results in observable acute cellular-pore generation (resealing time < 2 min) and, more importantly, generates intercellular gaps between adjacent confluent HUVECs that persist over longer timescales (~30-60 min). Confocal-microscopy/cell-viability assays repeatedly confirmed that the cultured endothelial cells remained viable at 40-min post-ultrasound transmission, suggesting a visible mechanism for these authors' findings of prolonged, enhanced vascular permeability (Helfield et al 2016) --and again documenting that the ultrasound/microbubble-mediated opening of the BBB can be considered temporary, reversible, and apparently safe (Aryal et al 2014;Dasgupta et al 2016;Helfield et al 2016;van Rooij et al 2016;Xie et al 2008).…”

Section: Implementation Of Supplementary Neurotherapy Using Targeted mentioning

confidence: 65%

“…Because the circulating microbubbles appear to concentrate the ultrasound effects to the blood vessel walls, the temporary opening of the BBB occurs through widening of tight junctions between endothelial cells (and possibly also activation of transcellular mechanisms) with little effect on the surrounding brain parenchyma (Aryal et al 2014;Dasgupta et al 2016;Xie et al 2008). This observed increase of BBB permeability is transient (i.e., the induced opening of the BBB is reversible) and apparently safe (Aryal et al 2014;Xie et al 2008), which is further supported by related cell-culture studies demonstrating viability of endothelial cells after ultrasound/microbubble-mediated sonoporation (Helfield et al 2016;van Rooij et al 2016). In particular, using human [umbilical vein] endothelial cell (HUVEC) monolayer cultures (Helfield et al 2016), it was found that ultrasound/microbubble-mediated sonoporation results in observable acute cellular-pore generation (resealing time < 2 min) and, more importantly, generates intercellular gaps between adjacent confluent HUVECs that persist over longer timescales (~30-60 min).…”

Section: Implementation Of Supplementary Neurotherapy Using Targeted mentioning

confidence: 69%

Nanotherapy for Alzheimer's disease and vascular dementia: Targeting senile endothelium

D'Arrigo

2018

Advances in Colloid and Interface Science

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Due to the complexity of Alzheimer's disease, multiple cellular types need to be targeted simultaneously in order for a given therapy to demonstrate any major effectiveness. Ultrasound-sensitive coated microbubbles (in a targeted lipid nanoemulsion) are available. Versatile small molecule drug(s) targeting multiple pathways of Alzheimer's disease pathogenesis are known. By incorporating such drug(s) into the targeted LCM/ND lipid nanoemulsion type, one obtains a multitasking combination therapeutic for translational medicine. This multitasking therapeutic targets cell-surface scavenger receptors (mainly SR-BI), making possible for various Alzheimer's-related cell types to be simultaneously searched out for localized drug treatment in vivo. Besides targeting cell-surface SR-BI, the proposed LCM/ND-nanoemulsion combination therapeutic(s) include a characteristic lipid-coated microbubble [LCM] subpopulation (i.e., a stable LCM suspension); such filmstabilized microbubbles are well known to substantially reduce the acoustic power levels needed for accomplishing temporary noninvasive (transcranial) ultrasound treatment, or sonoporation, if additionally desired for the Alzheimer's patient.

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Viability of endothelial cells after ultrasound-mediated sonoporation: Influence of targeting, oscillation, and displacement of microbubbles

Cited by 80 publications

References 61 publications

Theranostic Performance of Acoustic Nanodroplet Vaporization-Generated Bubbles in Tumor Intertissue

Theranostic Performance of Acoustic Nanodroplet Vaporization-Generated Bubbles in Tumor Intertissue

Sonoselective transfection of cerebral vasculature without blood–brain barrier disruption

Nanotherapy for Alzheimer's disease and vascular dementia: Targeting senile endothelium

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