Zugriffsnummer 37985
Dokumenttyp Zeitschriftenartikel Open Access Gold
Peer Review mit Peer Review
Sprache Englisch
Titel Targeting of magnetic nanoparticle-coated microbubbles to the vascular wall empowers site-specific lentiviral gene delivery in vivo
Autor(in); Institution
Heun, Y.; Walter Brendel Centre of Experimental Medicine, BMC, Ludwig-Maximilians-University, Planegg, GERMANY; DZHK (German Center for Cardiovascular Research) partner site Munich Heart Alliance, Munich, GERMANY
Hildebrand, S.; Institute of Pharmacology and Toxicology, Biomedical Center University of Bonn, Bonn, GERMANY
Heidsieck, A.; Central Institute of Medical Engineering (IMETUM), Technical University Munich, Garching, GERMANY
Gleich, B.; Central Institute of Medical Engineering (IMETUM), Technical University Munich, Garching, GERMANY
Anton, M.; Institute of Experimental Oncology and Therapy Research, Technical University Munich, Munich, GERMANY
Pircher, J.; Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Munich, GERMANY; Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, GERMANY
Ribeiro, A.; Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, GERMANY
Mykhaylyk, O.; Institute of Experimental Oncology and Therapy Research, Technical University Munich, Munich, GERMANY
Eberbeck, Dietmar; 8.2, Biosignale, PTB-Berlin
Wenzel, D.; Institute of Physiology I, Life&Brain Center, University Clinic Bonn, Bonn, GERMANY
Pfeifer, A.; Institute of Pharmacology and Toxicology, Biomedical Center University of Bonn, Bonn, GERMANY
Woernle, M.; Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, GERMANY
Krötz, F.; Invasive Cardiology, Starnberg Community Hospital, Starnberg, GERMANY
Pohl, U.; Walter Brendel Centre of Experimental Medicine, BMC, Ludwig-Maximilians-University, Planegg, GERMANY; DZHK (German Center for Cardiovascular Research) partner site Munich Heart Alliance, Munich, GERMANY; Munich cluster for systems neurology, (SyNergy) Munich, GERMANY
Mannell, H.; Walter Brendel Centre of Experimental Medicine, BMC, Ludwig-Maximilians-University, Planegg, GERMANY; DZHK (German Center for Cardiovascular Research) partner site Munich Heart Alliance, Munich, GERMANY
Quelle/Jahr Theranostics: 7 (2017), 2, 295 - 307
Availability [online only]
ISSN 1838-7640 (ONLINE)
DOI
Verlag Wyoming, NSW: Ivyspring International Publisher
Freie Schlagworte lentiviral gene delivery ; magnetic targeting ; ultrasound ; magnetic microbubbles ; VEGF ; endothelial cells
Zusammenfassung 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.
Kostenfreier Zugang Open Access Gold
Rechteinformation CC BY-NC 4.0 ; Creative Commons Attribution NonCommercial 4.0 License ; Original article under: Creative Commons Attribution (CC BY-NC) License

Zitierung

Heun, Y., Hildebrand, S., Heidsieck, A., Gleich, B., Anton, M., Pircher, J., Ribeiro, A., Mykhaylyk, O., Eberbeck, D., Wenzel, D., Pfeifer, A., Woernle, M., Krötz, F., Pohl, U., & Mannell, H. (2017). Targeting of magnetic nanoparticle-coated microbubbles to the vascular wall empowers site-specific lentiviral gene delivery in vivo. Theranostics, 7(2), 295–307. https://doi.org/10.7150/thno.16192

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