Targeted tumor theranostics using folate-conjugated and camptothecin-loaded acoustic nanodroplets in a mouse xenograft model

Chen, Wei-Tsung; Kang, Shih‐Tsung; Lin, Jinn; Wang, Chung-Hsin; Chen, Ran‐Chou; Yeh, Chih‐Kuang

doi:10.1016/j.biomaterials.2015.02.122

Cited by 50 publications

(26 citation statements)

References 34 publications

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“…Clinically used US imaging system has also been induced to activate droplet vaporization by increasing MI, but it could not accurately control the ADV area and it may be induced in the whole sonication scope. 34 Different from the previous work to trigger phase transition by HIFU, an LIFU instrument that produced lower intensity and focused acoustic energy was used to precisely induce ADV in tumor area as the encapsulated PFP core required a relatively low threshold of phase transition, which would reduce the nonspecific droplet-to-bubble transition around tumor and minimize the damage to healthy tissues surrounding the targeted site simultaneously. The focal zone of LIFU could be accurately located within the tumor region so that the phase transition of nanodroplets was controllable.…”

Section: Discussionmentioning

confidence: 99%

<div>Low-intensity focused ultrasound (LIFU)-induced acoustic droplet vaporization in phase-transition perfluoropentane nanodroplets modified by folate for ultrasound molecular imaging</div>

Liu¹,

Shang²,

Wang³

et al. 2017

IJN

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The commonly used ultrasound (US) molecular probes, such as targeted microbubbles and perfluorocarbon emulsions, present a number of inherent problems including the conflict between US visualization and particle penetration. This study describes the successful fabrication of phase changeable folate-targeted perfluoropentane nanodroplets (termed FA-NDs), a novel US molecular probe for tumor molecular imaging with US. Notably, these FA-NDs can be triggered by low-intensity focused US (LIFU) sonication, providing excellent US enhancement in B-mode and contrast-enhanced US mode in vitro. After intravenous administration into nude mice bearing SKOV3 ovarian carcinomas, 1,1′-dioctadecyl-3,3,3′,3′ -tetramethylindotricarbocya-nine iodide-labeled FA-NDs were found to accumulate in the tumor region. FA-NDs injection followed by LIFU sonication exhibited remarkable US contrast enhancement in the tumor region. In conclusion, combining our elaborately developed FA-NDs with LIFU sonication provides a potential protocol for US molecular imaging in folate receptor-overexpressing tumors.

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Section: Discussionmentioning

confidence: 99%

<div>Low-intensity focused ultrasound (LIFU)-induced acoustic droplet vaporization in phase-transition perfluoropentane nanodroplets modified by folate for ultrasound molecular imaging</div>

Liu¹,

Shang²,

Wang³

et al. 2017

IJN

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“…This has previously shown great promise as an extravascular contrast agent for diagnostic and therapeutic ultrasound [6], [8], [22], [23], [24], [25], [26], including promise for eventual clinical translation [27], [28]. In this paper, we provide the first demonstration of its potential for photoacoustic imaging, and thus as a versatile three-mode agent.…”

Section: Introductionmentioning

confidence: 91%

Optically and acoustically triggerable sub-micron phase-change contrast agents for enhanced photoacoustic and ultrasound imaging

et al. 2017

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We demonstrate a versatile phase-change sub-micron contrast agent providing three modes of contrast enhancement: 1) photoacoustic imaging contrast, 2) ultrasound contrast with optical activation, and 3) ultrasound contrast with acoustic activation. This agent, which we name ‘Cy-droplet’, has the following novel features. It comprises a highly volatile perfluorocarbon for easy versatile activation, and a near-infrared optically absorbing dye chosen to absorb light at a wavelength with good tissue penetration. It is manufactured via a ‘microbubble condensation’ method. The phase-transition of Cy-droplets can be optically triggered by pulsed-laser illumination, inducing photoacoustic signal and forming stable gas bubbles that are visible with echo-ultrasound in situ. Alternatively, Cy-droplets can be converted to microbubble contrast agents upon acoustic activation with clinical ultrasound. Potentially all modes offer extravascular contrast enhancement because of the sub-micron initial size. Such versatility of acoustic and optical ‘triggerability’ can potentially improve multi-modality imaging, molecularly targeted imaging and controlled drug release.

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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%

“…To obtain cytotoxicity with droplet vaporisation, previous studies have combined anti-cancer drugs such as doxorubicin with droplets3234. Marshalek et al 36.…”

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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Targeted tumor theranostics using folate-conjugated and camptothecin-loaded acoustic nanodroplets in a mouse xenograft model

Cited by 50 publications

References 34 publications

<div>Low-intensity focused ultrasound (LIFU)-induced acoustic droplet vaporization in phase-transition perfluoropentane nanodroplets modified by folate for ultrasound molecular imaging</div>

<div>Low-intensity focused ultrasound (LIFU)-induced acoustic droplet vaporization in phase-transition perfluoropentane nanodroplets modified by folate for ultrasound molecular imaging</div>

Optically and acoustically triggerable sub-micron phase-change contrast agents for enhanced photoacoustic and ultrasound imaging

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

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