Site directed vascular gene delivery in vivo by ultrasonic destruction of magnetic nanoparticle coated microbubbles

Mannell, Hanna; Pircher, Joachim; Fochler, Franziska; Stampnik, Yvonn; Räthel, Thomas; Gleich, Bernhard; Plank, Christian; Mykhaylyk, Olga; Dahmani, Chiheb; Wörnle, Markus; Ribeiro, Andrea; Pohl, Ulrich; Krötz, Florian

doi:10.1016/j.nano.2012.03.007

Cited by 32 publications

(21 citation statements)

References 35 publications

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“…13,27,[31][32][33] However, the resultant rapid collapse of bubbles (that is, cavitation) may also damage surrounding tissues, such as the endothelium. [4][5][6][7] In addition, the synchronous burst release of drugs could exceed toxic limits.…”

Section: Drug Delivery To In Vitro Cell Culturesmentioning

confidence: 99%

Controlled nanoparticle release from stable magnetic microbubble oscillations

Gao

Chan

et al. 2016

NPG Asia Mater

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Magnetic microbubbles (MMBs) are microbubbles (MBs) coated with magnetic nanoparticles (NPs). MMBs not only maintain the acoustic properties of MBs, but also serve as an important contrast agent for magnetic resonance imaging. Such dual-modality functionality makes MMBs particularly useful for a wide range of biomedical applications, such as localized drug/gene delivery. This article reports the ability of MMBs to release their particle cargo on demand under stable oscillation. When stimulated by ultrasound at resonant frequencies, MMBs of 450 nm to 200 μm oscillate in volume and surface modes. Above an oscillation threshold, NPs are released from the MMB shell and can travel hundreds of micrometers from the surface of the bubble. The migration of NPs from MMBs can be described with a force balance model. With this technology, we deliver doxorubicincontaining poly(lactic-co-glycolic acid) particles across a physiological barrier both in vitro and in vivo, with a 18-fold and 5-fold increase in NP delivery to the heart tissue of zebrafish and tumor tissue of mouse, respectively. The penetration of released NPs in tissues is also improved. The ability to remotely control the release of NPs from MMBs suggests opportunities for targeted drug delivery through/into tissues that are not easily diffused through or penetrated. NPG Asia Materials (2016) 8, e260; doi:10.1038/am.2016.37; published online 8 April 2016 INTRODUCTIONTargeted drug delivery and controlled release is the 'holy grail' of nanomedicine. In this regard, one emerging strategy employs a localized stimulus to precisely deposit drug-containing nanoparticles (NPs) at the tissue/organ of interest. The deposited NPs then continuously release drug molecules in a localized and sustained manner. Current strategies trigger the release of NPs from carriers via enzymes, 1 magnetic fields 2 and shear stress. 3 However, these methods are limited to specific organs/tissues, such as blocked blood vessels. A more versatile technology is desired that allows the targeted delivery of NPs to any organ/tissue while maintaining traceability using a non-invasive imaging modality.The present paper reports a strategy toward this end. Magnetic microbubbles (MMBs), the combination of multi-modal contrastenhanced imaging (both magnetic resonance imaging and ultrasound imaging) with targeted drug delivery (magnetic targeting) and controlled release (bubble cavitation) at any site of interest represents an emerging theranostic platform. However, the current formulations of MMBs, stabilized by a polymeric, lipid or silica shell, need a high acoustic energy field to trigger the release through bubble

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Section: Drug Delivery To In Vitro Cell Culturesmentioning

confidence: 99%

Controlled nanoparticle release from stable magnetic microbubble oscillations

Gao

Chan

et al. 2016

NPG Asia Mater

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“…Microbubbles can potentially be used as carriers for nanoscale US contrast agents and the incorporation of multimodal probes with potential therapeutic applications: sonodynamic therapy, ultrasound-induced apoptosis, sonoporation/sonotransfection, ultrasound-induced drug/gas delivery, and focused ultrasound-induced thermal ablation [32,33,280,[292][293][294][295][296][297][298][299].…”

Section: Ultrasound (Us)mentioning

confidence: 99%

Functionalized nanomaterials: their use as contrast agents in bioimaging: mono- and multimodal approaches

Trequesser¹,

Seznec²,

Delville³

2016

Nano Online

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The successful development of nanomaterials illustrates the considerable interest in the development of new molecular probes for medical diagnosis and imaging. Substantial progress was made in synthesis protocol and characterization of these materials whereas toxicological issues are sometimes incomplete. Nanoparticle-based contrast agents tend to become efficient tools for enhancing medical diagnostics and surgery for a wide range of 2 imaging modalities. Multimodal nanoparticles (NPs) are much more efficient than conventional molecular-scale contrast agents. They provide new abilities for in vivo detection and enhanced targeting efficiencies through longer circulation times, designed clearance pathways, and multiple binding capacities. Properly protected, they can safely be used for the fabrication of various functional systems with targeting properties, reduced toxicity and proper removal from the body. This review mainly describes the advances in the development of mono-to multimodal NPs and their in vitro and in vivo relevant biomedical applications ranging from imaging and tracking to cancer treatment. Besides specific applications for classical imaging, (MRI, PET, CT, US, PAI) are also mentioned less common imaging techniques such as terahertz molecular imaging (THMI) or ion beam analysis (IBA).Perspectives on multimodal theranostic NPs and their potential for clinical advances are also mentioned.

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“…The resulting magnetic microbubbles (MMB) represent an innovative and unique gene carrier system enabling localized magnetic accumulation of genetic vectors at the site of magnetic field (MF) exposure with simultaneous vector release and gene transfer induced by sonication. In previous work from our group we used MNP for targeted transfer of oligonucleotides to primary endothelial cells7,8 and recently we generated MMB and successfully proved their functionality as guidable carrier system for pDNA in vivo 9. To further improve gene transfer efficiency and transgene expression we established lentiviral MMB in a previous in vitro study10.…”

Section: Introductionmentioning

confidence: 99%

“…In this study, we thus evaluated a new type of lentiviral MMB containing silicon oxide-coated MNP (SO-Mag) with enhanced performance compared to our former established PEI-Mag MMB9,10 in terms of physico-chemical properties and gene transfer efficiency under static as well as flow conditions. Furthermore, we aimed to study whether our targeting system would be efficient to locally deliver genes to aortic endothelium ex vivo and to the microcirculation of mice in vivo upon systemic application.…”

Section: Introductionmentioning

confidence: 99%

Targeting of Magnetic Nanoparticle-coated Microbubbles to the Vascular Wall Empowers Site-specific Lentiviral Gene Delivery in vivo

Heun¹,

Hildebrand²,

Heidsieck³

et al. 2017

Theranostics

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In the field of vascular gene therapy, targeting systems are promising advancements to improve site-specificity of gene delivery. Here, we studied whether incorporation of magnetic nanoparticles (MNP) with different magnetic properties into ultrasound sensitive microbubbles may represent an efficient way to enable gene targeting in the vascular system after systemic application. Thus, we associated novel silicon oxide-coated magnetic nanoparticle containing microbubbles (SO-Mag MMB) with lentiviral particles carrying therapeutic genes and determined their physico-chemical as well as biological properties compared to MMB coated with polyethylenimine-coated magnetic nanoparticles (PEI-Mag MMB). While there were no differences between both MMB types concerning size and lentivirus binding, SO-Mag MMB exhibited superior characteristics regarding magnetic moment, magnetizability as well as transduction efficiency under static and flow conditions in vitro. Focal disruption of lentiviral SO-Mag MMB by ultrasound within isolated vessels exposed to an external magnetic field decisively improved localized VEGF expression in aortic endothelium ex vivo and enhanced the angiogenic response. Using the same system in vivo, we achieved a highly effective, site-specific lentiviral transgene expression in microvessels of the mouse dorsal skin after arterial injection. Thus, we established a novel lentiviral MMB technique, which has great potential towards site-directed vascular gene therapy.

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Site directed vascular gene delivery in vivo by ultrasonic destruction of magnetic nanoparticle coated microbubbles

Cited by 32 publications

References 35 publications

Controlled nanoparticle release from stable magnetic microbubble oscillations

Controlled nanoparticle release from stable magnetic microbubble oscillations

Functionalized nanomaterials: their use as contrast agents in bioimaging: mono- and multimodal approaches

Targeting of Magnetic Nanoparticle-coated Microbubbles to the Vascular Wall Empowers Site-specific Lentiviral Gene Delivery in vivo

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