Targeted and ultrasound-triggered cancer cell injury using perfluorocarbon emulsion-loaded liposomes endowed with cancer cell-targeting and fusogenic capabilities

Ninomiya, Kazuaki; Yamashita, Takahiro; Tanabe, Yoshihisa; Imai, Masamitsu; Takahashi, Kenji; Shimizu, Nobuaki

doi:10.1016/j.ultsonch.2015.06.032

Cited by 23 publications

(11 citation statements)

References 39 publications

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“…Cells receiving the formulation followed by US irradiation had their viability reduced to 43%, whereas cells receiving treatment with the formulation in the absence of US showed cell viability equal to 80%. Cell viability of those which received US-irradiation alone was about 80%, confirming that the US potentializes the formulation (65).…”

Section: Ultrasound-triggered Liposomesmentioning

confidence: 67%

Triggered Drug Release From Liposomes: Exploiting the Outer and Inner Tumor Environment

et al. 2021

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Since more than 40 years liposomes have being extensively studied for their potential as carriers of anticancer drugs. The basic principle behind their use for cancer treatment consists on the idea that they can take advantage of the leaky vasculature and poor lymphatic drainage present at the tumor tissue, passively accumulating in this region. Aiming to further improve their efficacy, different strategies have been employed such as PEGlation, which enables longer circulation times, or the attachment of ligands to liposomal surface for active targeting of cancer cells. A great challenge for drug delivery to cancer treatment now, is the possibility to trigger release from nanosystems at the tumor site, providing efficacious levels of drug in the tumor. Different strategies have been proposed to exploit the outer and inner tumor environment for triggering drug release from liposomes and are the focus of this review.

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Section: Ultrasound-triggered Liposomesmentioning

confidence: 67%

Triggered Drug Release From Liposomes: Exploiting the Outer and Inner Tumor Environment

et al. 2021

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“…Using dodecafluoropentane (DDFP) emulsion-loaded liposomes targeted to MCF-7 cells, Ninomiya et al provided evidence for ultrasound-mediated cell rupture, resulting in 43% cell viability after insonation [55]. Conjugation of a nuclear localization sequence [56] to the PCCA shell can promote migration of intracellular nanoparticles to the nucleus, thereby maximizing ultrasound-mediated therapeutic effects.…”

Section: Discussionmentioning

confidence: 99%

Intracellular delivery and ultrasonic activation of folate receptor-targeted phase-change contrast agents in breast cancer cells in vitro

Marshalek

Sheeran

Ingram

et al. 2016

Journal of Controlled Release

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Breast cancer is a diverse and complex disease that remains one of the leading causes of death among women. Novel, outside-of-the-box imaging and treatment methods are needed to supplement currently available technologies. In this study, we present evidence for the intracellular delivery and ultrasound-stimulated activation of folate receptor (FR)-targeted phase-change contrast agents (PCCAs) in MDA-MB-231 and MCF-7 breast cancer cells in vitro. PCCAs are lipid-coated, perfluorocarbon-filled particles formulated as nanoscale liquid droplets capable of vaporization into gaseous microbubbles for imaging or therapy. Cells were incubated with 1:1 decafluorobutane (DFB) / octafluoropropane (OFP) PCCAs for 1 hour, imaged via confocal microscopy, exposed to ultrasound (9 MHz, MI = 1.0 or 1.5), and imaged again after insonation. FR-targeted PCCAs were observed intracellularly in both cell lines, but uptake was significantly greater (p < 0.001) in MDA-MB-231 cells (93.0% internalization at MI = 1.0, 79.5% at MI = 1.5) than MCF-7 cells (42.4% internalization at MI = 1.0, 35.7% at MI = 1.5). Folate incorporation increased the frequency of intracellular PCCA detection 45-fold for MDA-MB-231 cells and 7-fold for MCF-7 cells, relative to untargeted PCCAs. Intracellularly activated PCCAs ranged from 500 nm to 6 microns (IQR = 800 nm – 1.5 microns) with a mean diameter of 1.15 ± 0.59 (SD) microns. The work presented herein demonstrates the feasibility of PCCA intracellular delivery and activation using breast cancer cells, illuminating a new platform toward intracellular imaging or therapeutic delivery with ultrasound.

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“…However, a cytotoxic effect could not be observed in their study. Ninomiya et al 37. investigated the targeting ability and cytotoxic effect of anti-cancer drug-free liposomes containing nano-emulsions of perfluoropentane.…”

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 and ultrasound-triggered cancer cell injury using perfluorocarbon emulsion-loaded liposomes endowed with cancer cell-targeting and fusogenic capabilities

Cited by 23 publications

References 39 publications

Triggered Drug Release From Liposomes: Exploiting the Outer and Inner Tumor Environment

Triggered Drug Release From Liposomes: Exploiting the Outer and Inner Tumor Environment

Intracellular delivery and ultrasonic activation of folate receptor-targeted phase-change contrast agents in breast cancer cells in vitro

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

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