Targeting of VEGF-mediated angiogenesis to rat myocardium using ultrasonic destruction of microbubbles

Korpanty, Grzegorz; Chen, S; Shohet, Ralph V.; Ding, Jindong; Yang, Bing; Frenkel, Peter A.; Grayburn, Paul A.

doi:10.1038/sj.gt.3302532

Cited by 117 publications

(80 citation statements)

References 44 publications

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“…Most in vivo studies have concentrated on organs and tissues that are readily imaged by diagnostic ultrasound machines, including skeletal muscle, heart and kidneys. 35,36,[48][49][50][51][52][53][54][55][56][57][58][59][60][61][62] Table 1 summarizes the results of some recent studies in these tissues using reporter genes, 35,36,[48][49][50][51][52][53][54]58,60,61 and broadly similar data have begun to emerge from studies in the vascular, 4,63,64 neurology 65-67 and oncology 18,37,68 fields, the pancreas 69 and in hematology. 70 On first inspection the relatively modest enhancements in plasmid-mediated transfection after USE in vivo may appear disappointing compared with the results obtained in vitro.…”

Section: Multiple Biophysical Effects Of Ultrasound May Contribute Tomentioning

confidence: 75%

Gene therapy progress and prospects: Ultrasound for gene transfer

2007

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Section: Multiple Biophysical Effects Of Ultrasound May Contribute Tomentioning

confidence: 75%

Gene therapy progress and prospects: Ultrasound for gene transfer

2007

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“…The applications of UCAs have recently expanded to include targeted imaging, thrombolysis, and drug and gene delivery (Dayton et al 1999;Hynynen et al 2001;Bloch et al 2004;Korpanty et al 2005;Chappell and Price 2006). In an ultrasound-assisted drug delivery system, the encapsulating shell prolongs the circulation time and the gas core increases the effect of ultrasound on the vehicle.…”

Section: Introductionmentioning

confidence: 99%

Acoustic response of compliable microvessels containing ultrasound contrast agents

2006

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The existing models of the dynamics of ultrasound contrast agents (UCAs) have largely been focused on an UCA surrounded by an infinite liquid. Preliminary investigations of a microbubble's oscillation in a rigid tube have been performed using linear perturbation, under the assumption that the tube diameter is significantly larger than UCA size. In the potential application of drug and gene delivery, it may be desirable to fragment the agent shell within small blood vessels and in some cases to rupture the vessel wall, releasing drugs and genes at the site. The effect of a compliant small blood vessel on the UCA's oscillation and the microvessel's acoustic response are unknown. The aim of this work is to propose a lumped-parameter model to study the interaction of a microbubble oscillation and compliable microvessels. Numerical results demonstrate that in the presence of UCAs, the transmural pressure through the blood vessel substantially increases and thus the vascular permeability is predicted to be enhanced. For a microbubble within an 8 to 40 micron vessel with a peak negative pressure of 0.1MPa and a center frequency of 1MHz, small changes in the microbubble oscillation frequency and maximum diameter are observed. When the ultrasound pressure increases, strong nonlinear oscillation occurs, with an increased circumferential stress on the vessel. For a compliable vessel with the range of diameters considered in this work, 0.2 MPa PNP at 1 MHz is predicted to be sufficient for microbubble fragmentation regardless the vessel diameter, however, for a rigid vessel 0.5 MPa PNP at 1 MHz may not be sufficient to fragment the bubbles. For a center frequency of 1MHz, a peak negative pressure of 0.5 MPa is predicted to be sufficient to exceed the stress threshold for vascular rupture in a small (diameter less than 15 μm) compliant vessel. As the vessel or surrounding tissue becomes more rigid, the UCA oscillation and vessel dilation decrease, however the circumferential stress is predicted to increase. Decreasing the vessel size or the center frequency increases the circumferential stress. For the two frequencies considered in this work, the circumferential stress does not scale as the inverse of the square root of the acoustic frequency v a as in the Mechanical Index, but rather has a stronger frequency dependence, 1/v a .

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“…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).…”

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confidence: 99%

Spatiotemporally controlled single cell sonoporation

Fan

Liu

Mayer

et al. 2012

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

216

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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Targeting of VEGF-mediated angiogenesis to rat myocardium using ultrasonic destruction of microbubbles

Cited by 117 publications

References 44 publications

Gene therapy progress and prospects: Ultrasound for gene transfer

Gene therapy progress and prospects: Ultrasound for gene transfer

Acoustic response of compliable microvessels containing ultrasound contrast agents

Spatiotemporally controlled single cell sonoporation

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