Optimal Enhancement Configuration of Silica Nanoparticles for Ultrasound Imaging and Automatic Detection at Conventional Diagnostic Frequencies

Casciaro, Sergio; Conversano, Francesco; Ragusa, Andrea; Malvindi, Maria Ada; Franchini, Roberto; Greco, Antonio; Pellegrino, Teresa; Gigli, Giuseppe

doi:10.1097/rli.0b013e3181e6f42f

Cited by 86 publications

(69 citation statements)

References 28 publications

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“…Research focusing on microbubbles as a drug delivery system and targetable compounds is rather limited and at an early stage of development, compared with the literature proposing CNTs as drug-delivery systems (3,(40)(41)(42). In addition, little work has been carried out on other types of nanomaterials and nanoparticles, including silica nanoparticles (43), iron oxide nanoparticles (44), and PEGylated nanocapsules (45) as possible ultrasound contrast agents. Aside from these studies, and keeping in mind possible future developments of nanoparticles acting as USCAs being able to target specific cells and deliver a drug, CNTs remain one of the most promising nanomaterials because of their extremely high aspect ratio (length/diameter ratio) and their easy capacity to penetrate cell membranes without exerting toxic effects.…”

Section: Discussionmentioning

confidence: 99%

Functionalized multiwalled carbon nanotubes as ultrasound contrast agents

Delogu

Vidili

Venturelli

et al. 2012

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

145

102

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Ultrasonography is a fundamental diagnostic imaging tool in everyday clinical practice. Here, we are unique in describing the use of functionalized multiwalled carbon nanotubes (MWCNTs) as hyperechogenic material, suggesting their potential application as ultrasound contrast agents. Initially, we carried out a thorough investigation to assess the echogenic property of the nanotubes in vitro. We demonstrated their long-lasting ultrasound contrast properties. We also showed that ultrasound signal of functionalized MWCNTs is higher than graphene oxide, pristine MWCNTs, and functionalized single-walled CNTs. Qualitatively, the ultrasound signal of CNTs was equal to that of sulfur hexafluoride (SonoVue), a commercially available contrast agent. Then, we found that MWCNTs were highly echogenic in liver and heart through ex vivo experiments using pig as an animal model. In contrast to the majority of ultrasound contrast agents, we observed in a phantom bladder that the tubes can be visualized within a wide variety of frequencies (i.e., 5.5–10 MHz) and 12.5 MHz using tissue harmonic imaging modality. Finally, we demonstrated in vivo in the pig bladder that MWCNTs can be observed at low frequencies, which are appropriate for abdominal organs. Importantly, we did not report any toxicity of CNTs after 7 d from the injection by animal autopsy, organ histology and immunostaining, blood count, and chemical profile. Our results reveal the enormous potential of CNTs as ultrasound contrast agents, giving support for their future applications as theranostic nanoparticles, combining diagnostic and therapeutic modalities.

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Section: Discussionmentioning

confidence: 99%

Functionalized multiwalled carbon nanotubes as ultrasound contrast agents

Delogu

Vidili

Venturelli

et al. 2012

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

145

102

View full text Add to dashboard Cite

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“…Particles in this size range, capable of retention within tumor vasculature, 47 can effectively attenuate ultrasound at theragnostic frequencies. 48 Further, DOTAP, a cationic lipid, likely conferred an affinity to the anionic endothelial glycocalyx. 49 This strong affinity for the vascular walls would decrease circulation time in vivo, 50 possibly necessitating local infusion, which would limit the applicability of NOBLs to tissues downstream from traditional intra-arterial access sites.…”

mentioning

confidence: 99%

Pulsed ultrasound enhances the delivery of nitric oxide from bubble liposomes to ex vivo porcine carotid tissue

Sutton¹,

Raymond²,

Verleye³

et al. 2014

IJN

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Ultrasound-mediated drug delivery is a novel technique for enhancing the penetration of drugs into diseased tissue beds noninvasively. By encapsulating drugs into microsized and nanosized liposomes, the therapeutic can be shielded from degradation within the vasculature until delivery to a target site by ultrasound exposure. Traditional in vitro or ex vivo techniques to quantify this delivery profile include optical approaches, cell culture, and electrophysiology. Here, we demonstrate an approach to characterize the degree of nitric oxide (NO) delivery to porcine carotid tissue by direct measurement of ex vivo vascular tone. An ex vivo perfusion model was adapted to assess ultrasound-mediated delivery of NO. This potent vasodilator was coencapsulated with inert octafluoropropane gas to produce acoustically active bubble liposomes. Porcine carotid arteries were excised post mortem and mounted in a physiologic buffer solution. Vascular tone was assessed in real time by coupling the artery to an isometric force transducer. NO-loaded bubble liposomes were infused into the lumen of the artery, which was exposed to 1 MHz pulsed ultrasound at a peak-to-peak acoustic pressure amplitude of 0.34 MPa. Acoustic cavitation emissions were monitored passively. Changes in vascular tone were measured and compared with control and sham NO bubble liposome exposures. Our results demonstrate that ultrasound-triggered NO release from bubble liposomes induces potent vasorelaxation within porcine carotid arteries (maximal relaxation 31%±8%), which was significantly stronger than vasorelaxation due to NO release from bubble liposomes in the absence of ultrasound (maximal relaxation 7%±3%), and comparable with relaxation due to 12 μM sodium nitroprusside infusions (maximal relaxation 32%±3%). This approach is a valuable mechanistic tool for assessing the extent of drug release and delivery to the vasculature caused by ultrasound.

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“…[9][10][11] These silica-coated fluorescent magnetic nanoprobes enabled development of biomedical platforms for simultaneous imaging, diagnosis, and therapy. [12][13][14] However, it is still a challenge to fabricate fluorescent magnetic nanoprobes with high photostability, high payloads of dye, and desirable outer surfaces for further modification with functional or target moieties.…”

Section: Introductionmentioning

confidence: 99%

VCAM-1-targeted core/shell nanoparticles for selective adhesion and delivery to endothelial cells with lipopolysaccharide-induced inflammation under shear flow and cellular magnetic resonance imaging in vitro

Yang¹,

Zhao²,

Liu³

et al. 2013

IJN

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Multifunctional nanomaterials with unique magnetic and luminescent properties have broad potential in biological applications. Because of the overexpression of vascular cell adhesion molecule-1 (VCAM-1) receptors in inflammatory endothelial cells as compared with normal endothelial cells, an anti-VCAM-1 monoclonal antibody can be used as a targeting ligand. Herein we describe the development of multifunctional core-shell Fe 3 O 4 @SiO 2 nanoparticles with the ability to target inflammatory endothelial cells via VCAM-1, magnetism, and fluorescence imaging, with efficient magnetic resonance imaging contrast characteristics. Superparamagnetic iron oxide and fluorescein isothiocyanate (FITC) were loaded successfully inside the nanoparticle core and the silica shell, respectively, creating VCAM-1-targeted Fe 3 O 4 @ SiO 2 (FITC) nanoparticles that were characterized by scanning electron microscopy, transmission electron microscopy, fluorescence spectrometry, zeta potential assay, and fluorescence microscopy. The VCAM-1-targeted Fe 3 O 4 @SiO 2 (FITC) nanoparticles typically had a diameter of 355 ± 37 nm, showed superparamagnetic behavior at room temperature, and cumulative and targeted adhesion to an inflammatory subline of human umbilical vein endothelial cells (HUVEC-CS) activated by lipopolysaccharide. Further, our data show that adhesion of VCAM-1-targeted Fe 3 O 4 @SiO 2 (FITC) nanoparticles to inflammatory HUVEC-CS depended on both shear stress and duration of exposure to stress. Analysis of internalization into HUVEC-CS showed that the efficiency of delivery of VCAM-1-targeted Fe 3 O 4 @SiO 2 (FITC) nanoparticles was also significantly greater than that of nontargeted Fe 3 O 4 @SiO 2 (FITC)-NH 2 nanoparticles. Magnetic resonance images showed that the superparamagnetic iron oxide cores of the VCAM-1-targeted Fe 3 O 4 @SiO 2 (FITC) nanoparticles could also act as a contrast agent for magnetic resonance imaging. Taken together, the cumulative adhesion and uptake potential of these VCAM-1-targeted Fe 3 O 4 @SiO 2 (FITC) nanoparticles targeted to inflammatory endothelial cells could be used in the transfer of therapeutic drugs/genes into these cells or for diagnosis of vascular disease at the molecular and cellular levels in the future.

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Optimal Enhancement Configuration of Silica Nanoparticles for Ultrasound Imaging and Automatic Detection at Conventional Diagnostic Frequencies

Cited by 86 publications

References 28 publications

Functionalized multiwalled carbon nanotubes as ultrasound contrast agents

Functionalized multiwalled carbon nanotubes as ultrasound contrast agents

Pulsed ultrasound enhances the delivery of nitric oxide from bubble liposomes to ex vivo porcine carotid tissue

VCAM-1-targeted core/shell nanoparticles for selective adhesion and delivery to endothelial cells with lipopolysaccharide-induced inflammation under shear flow and cellular magnetic resonance imaging in vitro

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