Sonic activation of molecularly-targeted nanoparticles accelerates transmembrane lipid delivery to cancer cells through contact-mediated mechanisms: Implications for enhanced local drug delivery

Crowder, Kathryn C.; Hughes, Michael S.; Marsh, Jon N.; Barbieri, Alejandro M.; Fuhrhop, Ralph W.; Lanza, Gregory M.; Wickline, Samuel A.

doi:10.1016/j.ultrasmedbio.2005.07.022

Cited by 64 publications

(60 citation statements)

References 32 publications

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“…29,30 We have termed this mechanism "contact facilitated drug delivery." 16,31 By comparison, significant antineovascular effects were not observed for control ␣ ␤ 3 integrin-targeted nanoparticles nor for nontargeted fumagillin nanoparticles.…”

Section: Discussionmentioning

confidence: 99%

Endothelial α _ν β ₃ Integrin–Targeted Fumagillin Nanoparticles Inhibit Angiogenesis in Atherosclerosis

Winter

Neubauer

Caruthers

et al. 2006

ATVB

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364

302

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Objective-Angiogenic expansion of the vasa vasorum is a well-known feature of progressive atherosclerosis, suggesting that antiangiogenic therapies may stabilize or regress plaques. ␣ ␤ 3 Integrin-targeted paramagnetic nanoparticles were prepared for noninvasive assessment of angiogenesis in early atherosclerosis, for site-specific delivery of antiangiogenic drug, and for quantitative follow-up of response. Methods and Results-Expression of ␣ ␤ 3 integrin by vasa vasorum was imaged at 1.5 T in cholesterol-fed rabbit aortas using integrin-targeted paramagnetic nanoparticles that incorporated fumagillin at 0 g/kg or 30 g/kg. Both formulations produced similar MRI signal enhancement (16.7%Ϯ1.1%) when integrated across all aortic slices from the renal arteries to the diaphragm. Seven days after this single treatment, integrin-targeted paramagnetic nanoparticles were readministered and showed decreased MRI enhancement among fumagillin-treated rabbits (2.9%Ϯ1.6%) but not in untreated rabbits (18.1%Ϯ2.1%). In a third group of rabbits, nontargeted fumagillin nanoparticles did not alter vascular ␣ ␤ 3 -integrin expression (12.4%Ϯ0.9%; PϾ0.05) versus the no-drug control. In a second study focused on microscopic changes, fewer microvessels in the fumagillin-treated rabbit aorta were counted compared with control rabbits. Conclusions-This study illustrates the potential of combined molecular imaging and drug delivery with targeted nanoparticles to noninvasively define atherosclerotic burden, to deliver effective targeted drug at a fraction of previous levels, and to quantify local response to treatment. Key Words: magnetic resonance imaging Ⅲ atherosclerosis Ⅲ molecular imaging Ⅲ angiogenesis Ⅲ nanoparticles Ⅲ fumagillin A key feature of the atherosclerotic process is the angiogenic expansion of the vasa vasorum in the adventitia, which extends into the thickening intimal layer of the atheroma in concert with other neovessels originating from the primary arterial lumen. 1 Extensive neovascular proliferation within atherosclerotic plaques is prominent within "culprit" lesions clinically associated with unstable angina, myocardial infarction, and stroke. [2][3][4] Plaque angiogenesis has been suggested to promote plaque growth, intraplaque hemorrhage, 5 and lesion instability.Magnetic resonance (MR) molecular imaging of focal angiogenesis in vivo with integrin-targeted paramagnetic contrast agents was reported with perfluorocarbon nanoparticles 6 -8 and liposomes. 9 Subsequently, we have developed MRI and postprocessing techniques to permit molecular imaging of the diffuse proliferating neovasculature associated with atherosclerotic plaque development. 10,11 The widespread expression of ␣ ␤ 3 integrins observed by MR agreed with the diffuse nature of angiogenesis microscopically observed in the early atherosclerotic aortas of cholesterol-fed rabbits.The importance of angiogenesis in the progression of atherosclerotic plaque combined with the antiangiogenic impact of 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase ...

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Section: Discussionmentioning

confidence: 99%

Endothelial α _ν β ₃ Integrin–Targeted Fumagillin Nanoparticles Inhibit Angiogenesis in Atherosclerosis

Winter

Neubauer

Caruthers

et al. 2006

ATVB

Self Cite

364

302

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“…84,87 Furthermore, extended efforts are ongoing to integrate therapeutic agents, such as antiproliferative drugs and gene transfection agents, into these ligand-targeted ultrasound contrast systems. 88 Similarly, several tissue/biology-specific MRI contrast agents are currently under development that can be created by attaching an affinity ligand to a magnetic compound, such as nanoparticles with gadolinium chelates or superparamagnetic particles of iron oxide (SPIOs). Finally, in vivo imaging of enzymatic activities has considerable clinical and scientific potential, because several families of proteases play crucial roles in both the progression and complications of atherosclerosis.…”

Section: Molecular Imaging With Targeted Agentsmentioning

confidence: 99%

Frontiers in Intravascular Imaging Technologies

Honda

Fitzgerald

2008

Circulation

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I n 1971, Bom et al 1 developed one of the first catheterbased real-time imaging techniques for use in the cardiac system. In placing a set of phased-array ultrasound transducers within the cardiac chambers, Bom and colleagues showed that higher frequencies than those used in transthoracic ultrasound imaging could be used to produce high-resolution images of cardiac structures. By the late 1980s, Yock et al 2 had successfully miniaturized a single-transducer system to enable transducer placement within coronary arteries. Since then, intravascular ultrasound (IVUS) has become a pivotal catheter-based imaging technology, having provided practical guidance for percutaneous interventions and scientific insights into vascular biology in clinical settings. Technical developments currently being explored consist of further device improvements, a variety of advanced image analyses, and the extension of this ultrasound-based approach to diverse intravascular imaging techniques with other energy sources. Principles and Device DevelopmentsUltrasound-Based Approaches IVUS systems produce tomographic images by performing a series of pulse/echo sequences, or vectors, in which an acoustic pulse is emitted and the subsequent reflections from the tissue are detected. Each vector is acquired by directing the ultrasound beam from the catheter in a slightly different direction from the previous vector by mechanical or electrical means. A gray-scale IVUS image is made with all the vectors (commonly 256 vectors), with each vector acquired at a different angle of rotation.Several clinically relevant properties of the ultrasound image, such as the resolution, depth of penetration and attenuation of the acoustic pulse by tissue, are dependent on the geometric and frequency properties of the transducer. A crystal transducer emits a signal that spans a range of frequencies. The higher the center frequency, the better the radial resolution (Figure 1) but the lower the depth of penetration. Conventional IVUS catheters used in the coronary arteries have center frequencies that range from 20 MHz to 40 MHz, thus providing theoretical lower limits of resolution (calculated as half the wavelength) of 39 and 19 m, respectively. In practice, the radial resolution is at least 2 to 5 times poorer, as determined by factors such as the length of the emitted pulse and the position of the imaged structures relative to the transducer.For peripheral and intracardiac echocardiographic (ICE) applications, larger imaging catheters with lower center frequencies (8 to 20 MHz) are produced in both mechanical and electrical configurations. In addition, a phased-array intracardiac echocardiography catheter is available that provides a sector image with color/spectral Doppler and multiple frequency imaging (5.0 to 10 MHz) capabilities. Optical Approaches AngioscopyIntracoronary angioscopy is an endoscopic technology that allows direct visualization of the surface color and superficial morphology of atherosclerotic plaque, thrombus, neointima, or stent struts. The ...

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“…Crowder et al (88) showed that the acoustic radiation force was the physical mechanism for the augmentation of lipid delivery from nanoparticles. The acoustic energy, at a noncavitational level, stimulates increased interaction between the nanoparticle's lipid layer and the targeted cell's plasma membrane and thereby improves transport of the drugs.…”

Section: Ultrasound-facilitated Drug Deliverymentioning

confidence: 99%

The role of ultrasound and magnetic resonance in local drug delivery

Deckers

Rome

Moonen

2008

Magnetic Resonance Imaging

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Local drug delivery has recently attracted much attention since it represents a strategy to increase the drug concentration at the target location and decrease systemic toxicity effects. Ultrasound can be used in different ways to trigger regional drug delivery. It can cause the local drug release from a carrier vehicle and the local increase of cell membrane permeability either by a mechanical action or by a temperature increase. Ultrasound contrast agents may enhance these effects by means of cavitation. Ultrasound can be focused deep inside the body into a small region with dimensions on the order of 1 mm. Several types of drug microcarriers have been proposed, from nano-to micrometer sized particles. The objective of real-time imaging of local drug delivery is to assure that the delivery takes place in the target region, that the drug concentration and the resulting physiological reaction are sufficient, and to intervene if necessary. Ultrasound and nuclear imaging techniques play an important role. MRI is rather insensitive but allows precise targeting of (focused) ultrasound, can provide real-time temperature maps, and gives access to a variety of imaging biomarkers that may be used to assess drug action. Examples from recent articles illustrate the potential of the principles of ultrasound-triggered local drug delivery.

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Sonic activation of molecularly-targeted nanoparticles accelerates transmembrane lipid delivery to cancer cells through contact-mediated mechanisms: Implications for enhanced local drug delivery

Cited by 64 publications

References 32 publications

Endothelial α _ν β ₃ Integrin–Targeted Fumagillin Nanoparticles Inhibit Angiogenesis in Atherosclerosis

Endothelial α _ν β ₃ Integrin–Targeted Fumagillin Nanoparticles Inhibit Angiogenesis in Atherosclerosis

Frontiers in Intravascular Imaging Technologies

The role of ultrasound and magnetic resonance in local drug delivery

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Sonic activation of molecularly-targeted nanoparticles accelerates transmembrane lipid delivery to cancer cells through contact-mediated mechanisms: Implications for enhanced local drug delivery

Cited by 64 publications

References 32 publications

Endothelial α ν β 3 Integrin–Targeted Fumagillin Nanoparticles Inhibit Angiogenesis in Atherosclerosis

Endothelial α ν β 3 Integrin–Targeted Fumagillin Nanoparticles Inhibit Angiogenesis in Atherosclerosis

Frontiers in Intravascular Imaging Technologies

The role of ultrasound and magnetic resonance in local drug delivery

Contact Info

Product

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Endothelial α _ν β ₃ Integrin–Targeted Fumagillin Nanoparticles Inhibit Angiogenesis in Atherosclerosis

Endothelial α _ν β ₃ Integrin–Targeted Fumagillin Nanoparticles Inhibit Angiogenesis in Atherosclerosis