Ultrasound responsive doxorubicin-loaded microbubbles; towards an easy applicable drug delivery platform

Geers, Bart; Lentacker, Ine; Cool, Steven K.; Demeester, Joseph; Smedt, Stefaan C. De; Sanders, Niek N.

doi:10.1016/j.jconrel.2010.07.023

Cited by 10 publications

(8 citation statements)

References 4 publications

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“…The drug vehicles have been various dispersions e.g. temperature sensitive liposomes [26], bubbles [27] and perfluorocarbon emulsions [28]. The procedure is generally that the US-sensitive formulation is injected intravenously or in the target area and then the US is applied from an external source.…”

Section: Us In Drug Deliverymentioning

confidence: 99%

Ultrasound induced cancer immunotherapy

Unga

Hashida

2014

Advanced Drug Delivery Reviews

101

111

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Recently, the use of ultrasound (US) has been shown to have potential in cancer immunotherapy. High intensity focused US destruction of tumors may lead to immunity forming in situ in the body by immune cells being exposed to the tumor debris and immune stimulatory substances that are present in the tumor remains. Another way of achieving anti-cancer immune responses is by using US in combination with microbubbles and nanobubbles to deliver genes and antigens into cells. US leads to bubble destruction and the forces released to direct delivery of the substances into the cytoplasm of the cells thus circumventing the natural barriers. In this way tumor antigens and antigen-encoding genes can be delivered to immune cells and immune response stimulating genes can be delivered to cancer cells thus enhancing immune responses. Combination of bubbles with cell-targeting ligands and US provides an even more sophisticated delivery system whereby the therapy is not only site specific but also cell specific. In this review we describe how US has been used to achieve immunity and discuss the potential and possible obstacles in future development.

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Section: Us In Drug Deliverymentioning

confidence: 99%

Ultrasound induced cancer immunotherapy

Unga

Hashida

2014

Advanced Drug Delivery Reviews

101

111

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“…Unfortunately, its clinical utility has been limited in many settings because of its high toxicity. Various delivery systems for DOX have been devised with the objectives of enhancing antitumor efficacy and reducing systemic toxicity [17, 18]. We hypothesized that combining PTA with DOX using a single nanoconstruct that mediates simultaneous photothermal effect and drug release (photothermal-chemotherapy) would result in enhanced antitumor activity and reduced toxicity compared to chemotherapy alone.…”

Section: Introductionmentioning

confidence: 99%

Photothermal-chemotherapy with doxorubicin-loaded hollow gold nanospheres: A platform for near-infrared light-trigged drug release

You

Zhang

et al. 2012

Journal of Controlled Release

202

142

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Photothermal ablation (PTA) is an emerging technique that uses near-infrared (NIR) laser light-generated heat to destroy tumor cells. However, complete eradication of tumor cells with PTA is difficult because of uneven heat distribution in the treatment volume. We hypothesized that combining PTA with chemotherapy using a single multifunctional nanoconstruct that mediates simultaneous photothermal cell killing and drug release (photothermal-chemotherapy) would result in enhanced antitumor activity and reduced toxicity compared to chemotherapy alone. Doxorubicin (DOX) was loaded to hollow gold nanospheres (HAuNS) coated with polyethylene glycol (PEG). The pharmacokinetics and biodistribution of both DOX and HAuNS in the resulting nanoconstruct, DOX@PEG-HAuNS having different DOX:PEG:HAuNS ratios, were evaluated using dual isotope labeling techniques. The antitumor activity of DOX@PEG-HAuNS with DOX:PEG:HAuNS weight ratio of 1:3:1 (NP3) in combination with NIR laser was studied in vitro and in vivo using human MDA-MB-231 breast cancer and A2780 ovarian cancer cells. In vitro, NP3 mediated PTA of both cancer cells and DOX release upon NIR laser treatment. In vivo, NP3 showed slower clearance in blood and greater accumulation in tumors than free DOX. NP3-plus-NIR laser demonstrated greater antitumor activity than free DOX, NP3, or liposomal DOX. Moreover, NP3 displayed significantly decreased systemic toxicity compared to free DOX or liposomal DOX. Enhanced antitumor effect with NP3-plus-laser can be attributed to both the cytotoxic effect of DOX released from NP3 and the photothermal effect mediated by HAuNS. Slow release of DOX from NP3 in normal tissues contributed to reduced systemic toxicity. Photothermal-chemotherapy exemplified by a single-agent nanoconstruct NP3 is a promising approach to anticancer therapy.

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“…Examples of drug loading techniques include the incorporation of therapeutic agents into the microbubble shell, the formulation of multi‐layer vehicles containing drugs in a layer separate from the shell or gas core, or conjugation of drug‐loaded liposomes or nanoparticles directly to the microbubble surface (Figure ) . Several drugs which have been evaluated for microbubble delivery to date include, but are not limited to, paclitaxel, doxorubicin, rapamycin, and 10‐hydroxycamptothecin …”

Section: Therapeutic Applicationsmentioning

confidence: 99%

Current status and prospects for microbubbles in ultrasound theranostics

Martin¹,

Dayton²

2013

WIREs Nanomed Nanobiotechnol

121

105

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Encapsulated microbubbles have been developed over the past two decades to provide both improvements in imaging as well as new therapeutic applications. Microbubble contrast agents are used currently for clinical imaging where increased sensitivity to blood flow is required, such as echocardiography. These compressible spheres oscillate in an acoustic field, producing nonlinear responses which can be uniquely distinguished from surrounding tissue, resulting in substantial enhancements in imaging signal-to-noise ratio. Furthermore, with sufficient acoustic energy the oscillation of microbubbles can mediate localized biological effects in tissue including the enhancement of membrane permeability or increased thermal energy deposition. Structurally, microbubbles are comprised of two principal components – an encapsulating shell and an inner gas core. This configuration enables microbubbles to be loaded with drugs or genes for additional therapeutic effect. Application of sufficient ultrasound energy can release this payload, resulting in site-specific delivery. Extensive pre-clinical studies illustrate that combining microbubbles and ultrasound can result in enhanced drug delivery or gene expression at spatially selective sites. Thus, microbbubles can be used for imaging, for therapy, or for both simultaneously. In this sense, microbubbles combined with acoustics may be one of the most universal theranostic tools.

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Ultrasound responsive doxorubicin-loaded microbubbles; towards an easy applicable drug delivery platform

Cited by 10 publications

References 4 publications

Ultrasound induced cancer immunotherapy

Ultrasound induced cancer immunotherapy

Photothermal-chemotherapy with doxorubicin-loaded hollow gold nanospheres: A platform for near-infrared light-trigged drug release

Current status and prospects for microbubbles in ultrasound theranostics

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