Ultrasound, cavitation bubbles and their interaction with cells

Wu, Junru; Nyborg, Wesley L.

doi:10.1016/j.addr.2008.03.009

Cited by 463 publications

(349 citation statements)

References 38 publications

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“…26 Owing to the introduction of a shell elastic parameter and the shell friction factor of the NP shell, which ultimately increase the associated resonant frequencies, 27 the MMB resonant frequencies measured during these experiments are slightly larger than those obtained for MBs without NP coatings. We note that theoretically the mass loading from our NP shell is negligible.…”

Section: Oscillating Microbubbles For Nanoparticle Release Y Gao Et Almentioning

confidence: 86%

See 1 more Smart Citation

Controlled nanoparticle release from stable magnetic microbubble oscillations

Gao

Chan

et al. 2016

NPG Asia Mater

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Magnetic microbubbles (MMBs) are microbubbles (MBs) coated with magnetic nanoparticles (NPs). MMBs not only maintain the acoustic properties of MBs, but also serve as an important contrast agent for magnetic resonance imaging. Such dual-modality functionality makes MMBs particularly useful for a wide range of biomedical applications, such as localized drug/gene delivery. This article reports the ability of MMBs to release their particle cargo on demand under stable oscillation. When stimulated by ultrasound at resonant frequencies, MMBs of 450 nm to 200 μm oscillate in volume and surface modes. Above an oscillation threshold, NPs are released from the MMB shell and can travel hundreds of micrometers from the surface of the bubble. The migration of NPs from MMBs can be described with a force balance model. With this technology, we deliver doxorubicincontaining poly(lactic-co-glycolic acid) particles across a physiological barrier both in vitro and in vivo, with a 18-fold and 5-fold increase in NP delivery to the heart tissue of zebrafish and tumor tissue of mouse, respectively. The penetration of released NPs in tissues is also improved. The ability to remotely control the release of NPs from MMBs suggests opportunities for targeted drug delivery through/into tissues that are not easily diffused through or penetrated. NPG Asia Materials (2016) 8, e260; doi:10.1038/am.2016.37; published online 8 April 2016 INTRODUCTIONTargeted drug delivery and controlled release is the 'holy grail' of nanomedicine. In this regard, one emerging strategy employs a localized stimulus to precisely deposit drug-containing nanoparticles (NPs) at the tissue/organ of interest. The deposited NPs then continuously release drug molecules in a localized and sustained manner. Current strategies trigger the release of NPs from carriers via enzymes, 1 magnetic fields 2 and shear stress. 3 However, these methods are limited to specific organs/tissues, such as blocked blood vessels. A more versatile technology is desired that allows the targeted delivery of NPs to any organ/tissue while maintaining traceability using a non-invasive imaging modality.The present paper reports a strategy toward this end. Magnetic microbubbles (MMBs), the combination of multi-modal contrastenhanced imaging (both magnetic resonance imaging and ultrasound imaging) with targeted drug delivery (magnetic targeting) and controlled release (bubble cavitation) at any site of interest represents an emerging theranostic platform. However, the current formulations of MMBs, stabilized by a polymeric, lipid or silica shell, need a high acoustic energy field to trigger the release through bubble

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Section: Oscillating Microbubbles For Nanoparticle Release Y Gao Et Almentioning

confidence: 86%

“…13,27,[31][32][33] However, the resultant rapid collapse of bubbles (that is, cavitation) may also damage surrounding tissues, such as the endothelium. [4][5][6][7] In addition, the synchronous burst release of drugs could exceed toxic limits.…”

Section: Drug Delivery To In Vitro Cell Culturesmentioning

confidence: 99%

Controlled nanoparticle release from stable magnetic microbubble oscillations

Gao

Chan

et al. 2016

NPG Asia Mater

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“…Ultrasound application induces cavitation of the microbubbles (17), signified by rapid volume expansion/contraction and/or collapse (18). These effects generate localized fluid flow, shear stress, and other mechanical or physical impact capable of affecting cells and structures nearby (7,19,20).However, the detailed processes supporting sonoporationmediated transmembrane and transcellular transport are not well understood, particularly at the single-cell level. The absence of such mechanistic understanding hinders the successful development of the technology as an effective and safe strategy.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Spatiotemporally controlled single cell sonoporation

Fan

Liu

Mayer

et al. 2012

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

209

215

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This paper presents unique approaches to enable control and quantification of ultrasound-mediated cell membrane disruption, or sonoporation, at the single-cell level. Ultrasound excitation of microbubbles that were targeted to the plasma membrane of HEK-293 cells generated spatially and temporally controlled membrane disruption with high repeatability. Using whole-cell patch clamp recording combined with fluorescence microscopy, we obtained time-resolved measurements of single-cell sonoporation and quantified the size and resealing rate of pores. We measured the intracellular diffusion coefficient of cytoplasmic RNA/DNA from sonoporation-induced transport of an intercalating fluorescent dye into and within single cells. We achieved spatiotemporally controlled delivery with subcellular precision and calcium signaling in targeted cells by selective excitation of microbubbles. Finally, we utilized sonoporation to deliver calcein, a membrane-impermeant substrate of multidrug resistance protein-1 (MRP1), into HEK-MRP1 cells, which overexpress MRP1, and monitored the calcein efflux by MRP1. This approach made it possible to measure the efflux rate in individual cells and to compare it directly to the efflux rate in parental control cells that do not express MRP1.D espite the development of various approaches for transporting membrane-impermeant compounds (such as fluorescent markers, DNA, RNA, siRNA, proteins, peptides, and amino acids) into living cells (1-3), efficient intracellular delivery of bioactive agents for biomedical applications with minimal adverse effects remains challenging. In addition, it is desirable yet difficult to achieve local perturbation of intracellular processes, which requires subcellular molecular localization inside the living cell (4, 5).Sonoporation uses ultrasound to induce transient disruption of cell membranes (6-8), thereby enabling transport of membraneimpermeant compounds into the cytoplasm of living cells (6,(9)(10)(11). Without the need to use viral vectors, sonoporation enables the delivery of a wide range of bioactive agents with minimal inflammatory and immunological responses for both in vitro studies and in vivo applications (12-16). In addition, ultrasound application can be targeted to a specific volume of tissue in vivo noninvasively. These unique characteristics make sonoporation a compelling and versatile technology for nonviral drug and gene delivery.Sonoporation is typically performed for bulk treatment of a tissue volume in vivo or a large number of cells in vitro, often facilitated by microbubbles that are either injected in the vasculature or mixed in solution with suspended or attached cells. Ultrasound application induces cavitation of the microbubbles (17), signified by rapid volume expansion/contraction and/or collapse (18). These effects generate localized fluid flow, shear stress, and other mechanical or physical impact capable of affecting cells and structures nearby (7,19,20).However, the detailed processes supporting sonoporationmediated transmembrane and ...

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“…After pulses of many cycles, the USRF may push MBs to the targeted cells [24]. When a high-amplitude ultrasonic wave interacts with MBs, small pores in the cell membrane can form by a process called sonoporation [25,26]. The transit pores allow transport of compounds into the cytoplasm of living cells [27].…”

Section: Introductionmentioning

confidence: 99%

Altering the response of intracellular reactive oxygen to magnetic nanoparticles using ultrasound and microbubbles

Yang

Cui

et al. 2015

Sci. China Mater.

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Engineered iron oxide magnetic nanoparticles (MNPs) are one of the most promising tools in nanomedicine-based diagnostics and therapy. However, increasing evidence suggests that their specific delivery efficiency and potential long-term cytotoxicity remain a great concern. In this study, using 12 nm γ-Fe2O3 MNPs, we investigated three types of uptake pathways for MNPs into HepG2 cells: (1) a conventional incubation endocytic pathway; (2) MNPs co-administrated with microbubbles under ultrasound exposure; and (3) ultrasound delivery of MNPs covalently coated on the surface of microbubbles. The delivery efficiency and intracellular distribution of MNPs were evaluated, and the cytotoxicity induced by reactive oxygen species (ROS) was studied in detail. The results show that MNPs can be delivered into the lysosomes via classical incubation endocytic internalization; however, microbubbles and ultrasound allow the MNPs to pass through the cell membrane and enter the cytosol via a non-internalizing uptake route much more evenly and efficiently. Further, these different delivery routes result in different ROS levels and antioxidant capacities, as well as intracellular glutathione peroxidase activity for HepG2 cells. Our data indicate that the microbubble-ultrasound treatment method can serve as an efficient cytosolic delivery strategy to minimize long-term cytotoxicity of MNPs.

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Ultrasound, cavitation bubbles and their interaction with cells

Cited by 463 publications

References 38 publications

Controlled nanoparticle release from stable magnetic microbubble oscillations

Controlled nanoparticle release from stable magnetic microbubble oscillations

Spatiotemporally controlled single cell sonoporation

Altering the response of intracellular reactive oxygen to magnetic nanoparticles using ultrasound and microbubbles

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