Targeted microbubble mediated sonoporation of endothelial cells in vivo

Skachkov, Ilya; Luan, Ying; Steen, Antonius F.W. van der; Jong, Nico de; Kooiman, Klazina

doi:10.1109/tuffc.2014.006440

Cited by 38 publications

(32 citation statements)

References 49 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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“…This can be explained by the fact that chirp pulses cover a broader range of resonance frequencies, as MBs with various sizes have different resonance frequencies; chirp pulses are therefore more efficient than single frequency pulses. In the chicken embryo model (in vivo), a single sine-wave burst (1 MHz, 1000 cycles at 150 or 200 kPa) was sufficient for vascular PI uptake using a v b 3 -tUCA as shown in Figure 3(C) [183].…”

Section: Enhanced Drug Deliverymentioning

confidence: 99%

Targeted ultrasound contrast agents for ultrasound molecular imaging and therapy

Rooij

Daeichin

Skachkov

et al. 2015

International Journal of Hyperthermia

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Ultrasound contrast agents (UCAs) are used routinely in the clinic to enhance contrast in ultrasonography. More recently, UCAs have been functionalised by conjugating ligands to their surface to target specific biomarkers of a disease or a disease process. These targeted UCAs (tUCAs) are used for a wide range of pre-clinical applications including diagnosis, monitoring of drug treatment, and therapy. In this review, recent achievements with tUCAs in the field of molecular imaging, evaluation of therapy, drug delivery, and therapeutic applications are discussed. We present the different coating materials and aspects that have to be considered when manufacturing tUCAs. Next to tUCA design and the choice of ligands for specific biomarkers, additional techniques are discussed that are applied to improve binding of the tUCAs to their target and to quantify the strength of this bond. As imaging techniques rely on the specific behaviour of tUCAs in an ultrasound field, it is crucial to understand the characteristics of both free and adhered tUCAs. To image and quantify the adhered tUCAs, the state-of-the-art techniques used for ultrasound molecular imaging and quantification are presented. This review concludes with the potential of tUCAs for drug delivery and therapeutic applications.

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“…In addition, in vivo one can also study microbubble vibration when microbubbles are in contact with cells and under flow, for which the chorioallantoic membrane model could be used. This model has proven to be useful to study nontargeted microbubble vibration using ultrahigh-speed imaging and targeted-microbubble mediated drug delivery [47], [48].…”

Section: E Limitations and Outlookmentioning

confidence: 99%

Vibrational Responses of Bound and Nonbound Targeted Lipid-Coated Single Microbubbles

Rooij

Beekers

Lattwein

et al. 2017

IEEE Trans. Ultrason., Ferroelect., Freq. Contr.

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One of the main challenges for ultrasound molecular imaging is acoustically distinguishing nonbound microbubbles from those bound to their molecular target. In this in vitro study, we compared two types of in-house produced targeted lipid-coated microbubbles, either consisting of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, C16:0 (DPPC) or 1,2-distearoyl-sn-glycero-3-phosphocholine, C18:0 (DSPC) as the main lipid, using the Brandaris 128 ultrahigh-speed camera to determine vibrational response differences between bound and nonbound biotinylated microbubbles. In contrast to previous studies that studied vibrational differences upon binding, we used a covalently bound model biomarker (i.e., streptavidin) rather than physisorption, to ensure binding of the biomarker to the membrane. The microbubbles were insonified at frequencies between 1 and 4 MHz at pressures of 50 and 150 kPa. This paper shows lower acoustic stability of bound microbubbles, of which DPPC-based microbubbles deflated most. For DPPC microbubbles with diameters between 2 and [Formula: see text] driven at 50 kPa, resonance frequencies of bound microbubbles were all higher than 1.8 MHz, whereas those of nonbound microbubbles were significantly lower. In addition, the relative radial excursions at resonance were also higher for bound DPPC microbubbles. These differences did not persist when the pressure was increased to 150 kPa, except for the acoustic stability which further decreased. No differences in resonance frequencies were observed between bound and nonbound DSPC microbubbles. Nonlinear responses in terms of emissions at the subharmonic and second harmonic frequencies were similar for bound and nonbound microbubbles at both pressures. In conclusion, we identified differences in vibrational responses of bound DPPC microbubbles with diameters between 2 and [Formula: see text] that distinguish them from nonbound ones.

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Targeted microbubble mediated sonoporation of endothelial cells in vivo

Cited by 38 publications

References 49 publications

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

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

Targeted ultrasound contrast agents for ultrasound molecular imaging and therapy

Vibrational Responses of Bound and Nonbound Targeted Lipid-Coated Single Microbubbles

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