Superparamagnetic iron oxide and drug complex-embedded acoustic droplets for ultrasound targeted theranosis

Wang, Chung-Hsin; Kang, Shih‐Tsung; Yeh, Chih‐Kuang

doi:10.1016/j.biomaterials.2012.11.037

Cited by 43 publications

(36 citation statements)

References 40 publications

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“…An example of this is the use of nanoparticle labeled antivascular endothelial growth factor receptor (EGFR) antibodies for in vitro and in vivo magnetic resonance molecular imaging. This approach successfully visualized and differentiated C6 glioma tumor types based on their EGFR expression [25]. Intravenous application of labeled anti-EGFR in this same study resulted in a quick delivery to the tumor without the necessity to clear the tissue from adherent tissue or mucus.…”

Section: Acoustic Droplet Vaporization In Clinical Nanomedicinementioning

confidence: 91%

Acoustic Droplet Vaporization in Biology and Medicine

Lin

Pitt

2013

BioMed Research International

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This paper reviews the literature regarding the use of acoustic droplet vaporization (ADV) in clinical applications of imaging, embolic therapy, and therapeutic delivery. ADV is a physical process in which the pressure waves of ultrasound induce a phase transition that causes superheated liquid nanodroplets to form gas bubbles. The bubbles provide ultrasonic imaging contrast and other functions. ADV of perfluoropentane was used extensively in imaging for preclinical trials in the 1990s, but its use declined rapidly with the advent of other imaging agents. In the last decade, ADV was proposed and explored for embolic occlusion therapy, drug delivery, aberration correction, and high intensity focused ultrasound (HIFU) sensitization. Vessel occlusion via ADV has been explored in rodents and dogs and may be approaching clinical use. ADV for drug delivery is still in preclinical stages with initial applications to treat tumors in mice. Other techniques are still in preclinical studies but have potential for clinical use in specialty applications. Overall, ADV has a bright future in clinical application because the small size of nanodroplets greatly reduces the rate of clearance compared to larger contrast agent bubbles and yet provides the advantages of ultrasonographic contrast, acoustic cavitation, and nontoxicity of conventional perfluorocarbon contrast agent bubbles.

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Section: Acoustic Droplet Vaporization In Clinical Nanomedicinementioning

confidence: 91%

Acoustic Droplet Vaporization in Biology and Medicine

Lin

Pitt

2013

BioMed Research International

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“…Among these, the phase-change contrast agent (PCCA) has been proposed for a wide range of applications as a result of its unique functionality (Rapoport 2012, Sheeran and Dayton 2012). When generated at microscale and nanoscale sizes, perfluorocarbon-based PCCAs have shown preclinical promise as highly-dynamic agents for applications such as selective vascular occlusion (Kripfgans et al 2000, Kripfgans et al 2002, Kripfgans et al 2005, Zhang et al 2010), cavitation nucleation enhancement and acoustic ablation (Miller et al 2000, Zhang and Porter 2010, Zhang et al 2011, Phillips et al 2013), generation of in vivo contrast (Kripfgans et al 2000, Haworth et al 2008, Reznik et al 2011, Sheeran et al 2011b, Wang et al 2012b, Wang et al 2012a, Couture et al 2012, Sheeran et al 2013), therapeutic delivery (Rapoport et al 2009b, Fabiilli et al 2010b, Fabiilli et al 2010a, Rapoport et al 2011, Couture et al 2012, Javadi et al 2012, Lattin et al 2012), and integration with other imaging modalities (Rapoport et al 2011, Strohm et al 2011, Wilson et al 2012, Strohm et al 2012). The utility of PCCAs stems primarily from their ability to be used in both the liquid and gas states, and the use of a non-invasive modality (ultrasound) to trigger this transition both temporally and spatially.…”

Section: Introductionmentioning

confidence: 99%

Phase-transition thresholds and vaporization phenomena for ultrasound phase-change nanoemulsions assessed via high-speed optical microscopy

Sheeran¹,

Matsunaga²,

Dayton³

2013

Phys. Med. Biol.

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Ultrasonically activated phase-change contrast agents (PCCAs) based on perfluorocarbon droplets have been proposed for a variety of therapeutic and diagnostic clinical applications. When generated at the nanoscale, droplets may be small enough to exit the vascular space and then be induced to vaporize with high spatial and temporal specificity by externally-applied ultrasound. The use of acoustical techniques for optimizing ultrasound parameters for given applications can be a significant challenge for nanoscale PCCAs due to the contributions of larger outlier droplets. Similarly, optical techniques can be a challenge due to the sub-micron size of nanodroplet agents and resolution limits of optical microscopy. In this study, an optical method for determining activation thresholds of nanoscale emulsions based on the in vitro distribution of bubbles resulting from vaporization of PCCAs after single, short (<10 cycles) ultrasound pulses is evaluated. Through ultra-high-speed microscopy it is shown that the bubbles produced early in the pulse from vaporized droplets are strongly affected by subsequent cycles of the vaporization pulse, and these effects increase with pulse length. Results show that decafluorobutane nanoemulsions with peak diameters on the order of 200 nm can be optimally vaporized with short pulses using pressures amenable to clinical diagnostic ultrasound machines.

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“…Few studies have reported the conjugation of active targeting molecules to PFC droplets such as aptamer32, folate3334 and anti-vascular endothelial growth factor receptor 2 antibody with magnetism-assisted targeting35 in order to direct them to cancer cells. To obtain cytotoxicity with droplet vaporisation, previous studies have combined anti-cancer drugs such as doxorubicin with droplets3234.…”

Section: Discussionmentioning

confidence: 99%

Selective intracellular vaporisation of antibody-conjugated phase-change nano-droplets in vitro

Ishijima

Minamihata

Yamaguchi

et al. 2017

Sci Rep

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While chemotherapy is a major mode of cancer therapeutics, its efficacy is limited by systemic toxicities and drug resistance. Recent advances in nanomedicine provide the opportunity to reduce systemic toxicities. However, drug resistance remains a major challenge in cancer treatment research. Here we developed a nanomedicine composed of a phase-change nano-droplet (PCND) and an anti-cancer antibody (9E5), proposing the concept of ultrasound cancer therapy with intracellular vaporisation. PCND is a liquid perfluorocarbon nanoparticle with a liquid–gas phase that is transformable upon exposure to ultrasound. 9E5 is a monoclonal antibody targeting epiregulin (EREG). We found that 9E5-conjugated PCNDs are selectively internalised into targeted cancer cells and kill the cells dynamically by ultrasound-induced intracellular vaporisation. In vitro experiments show that 9E5-conjugated PCND targets 97.8% of high-EREG-expressing cancer cells and kills 57% of those targeted upon exposure to ultrasound. Furthermore, direct observation of the intracellular vaporisation process revealed the significant morphological alterations of cells and the release of intracellular contents.

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Superparamagnetic iron oxide and drug complex-embedded acoustic droplets for ultrasound targeted theranosis

Cited by 43 publications

References 40 publications

Acoustic Droplet Vaporization in Biology and Medicine

Acoustic Droplet Vaporization in Biology and Medicine

Phase-transition thresholds and vaporization phenomena for ultrasound phase-change nanoemulsions assessed via high-speed optical microscopy

Selective intracellular vaporisation of antibody-conjugated phase-change nano-droplets in vitro

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