Identification of Magnetic Nanoparticles for Combined Positioning and Lentiviral Transduction of Endothelial Cells

Wenzel, Daniela; Rieck, Sarah; Vosen, Sarah; Mykhaylyk, Olga; Trueck, Christina; Eberbeck, Dietmar; Trahms, Lutz; Zimmermann, Katrin; Pfeifer, Alexander; Fleischmann, Bernd K.

doi:10.1007/s11095-011-0657-5

Cited by 24 publications

(26 citation statements)

References 22 publications

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“…To determine the systemic distribution of MNP in lentiviral MMB treated mice, organs were isolated using non-metallic (iron-free) instruments, mechanically homogenized in PBS and exposed to magnetic particle spectroscopy (MPS) as described before 46.…”

Section: Methodsmentioning

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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Section: Methodsmentioning

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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“…RT‐PCR was performed as previously reported (18, 19). After homogenization with the TissueLyser LT (Qiagen, Hilden, Germany), total RNA was isolated from PAs and TRs by the RNeasy microkit (Qiagen).…”

Section: Methodsmentioning

confidence: 99%

RGD peptides induce relaxation of pulmonary arteries and airwaysviaβ3‐integrins

2014

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Novel relaxants of pulmonary arteries and airways are of special interest to obtain insights into pulmonary signaling pathways and to develop treatment strategies for lung diseases. Herein, we demonstrate that Arg-Gly-Asp (RGD) peptides induce a dose-dependent relaxation of pulmonary arteries and airways in mouse. The relaxing effect was specific because it was strongly reduced using the control peptides RGE or RAD (P<0.001). Longer peptide sequences containing RGD and its flanking amino acids found in fibronectin showed a similar effect even at a 10-fold lower concentration. The relevance of RGD-induced pulmonary vasorelaxation was demonstrated in isometric force measurements, lung slices, and the isolated perfused lung model under normoxia and hypoxia and in vivo. As cell surface receptor we identified β3- but not β1-integrin subunits. Moreover, vasorelaxation by RGD peptides was strongly diminished after removal of the endothelium in endothelial nitric oxide synthase-deficient (eNOS(-/-) mice; P<0.01) and after pharmacological inhibition of the NO/sGC pathway (P<0.05). Additionally, several potassium channels like Kv, Kir, and KATP played a role. In airways the response was mediated by Kv and KCa channels. Thus, RGD peptides are relaxants of pulmonary arteries and airways. These findings may help to establish novel therapeutic approaches for pulmonary hypertension and obstructive lung disease.

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“…Immunostaining was performed as previously described (15). PAs were isolated, fixed in 4% paraformaldehyde overnight, embedded in Tissue-Tek, and frozen.…”

Section: Immunostainingmentioning

confidence: 99%

The β ₂ agonist terbutaline specifically decreases pulmonary arterial pressure under normoxia and hypoxia via a adrenoceptor antagonism

et al. 2018

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Pulmonary hypertension is a severe, incurable disease with a poor prognosis. Although treatment regimens have improved during the last 2 decades, current pharmacologic strategies are limited and focus on the modulation of only a few pathways related to endothelin, NO, and prostacyclin signaling. Therefore, the identification of novel molecular targets is urgently needed. We found that the β adrenoceptor (AR) agonists terbutaline (TER) and salbutamol induced a dose-dependent vasorelaxation in large pulmonary arteries but not aortas of mouse. This effect was found to be independent of β ARs and the endothelium but was determined by the type of the preconstrictor. Vasodilation by β AR agonists occurred after pretreatment of pulmonary arteries with phenylephrine and serotonin, both agonists of α ARs, but was absent after preconstriction with the thromboxane analog U46619. These data indicated α-adrenolytic activity of β AR agonists, which was confirmed by a right shift of the phenylephrine dose-response curve by TER. This effect was physiologically relevant because TER also relaxed small intrapulmonary arteries in lung slices and diminished pulmonary arterial pressure in an isolated perfused lung model under normoxia and hypoxia. Finally, TER applied as an aerosol also selectively decreased pulmonary arterial pressure without effects on systemic blood pressure and heart rate in mouse in vivo. Thus, β AR agonists display α-adrenolytic activity in pulmonary arteries ex vivo and in vivo, and may provide a novel option to reduce pulmonary arterial pressure in pulmonary hypertension.-Neumann, V., Knies, R., Seidinger, A., Simon, A., Lorenz, K., Matthey, M., Breuer, J., Wenzel, D. The β agonist terbutaline specifically decreases pulmonary arterial pressure under normoxia and hypoxia via α adrenoceptor antagonism.

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Identification of Magnetic Nanoparticles for Combined Positioning and Lentiviral Transduction of Endothelial Cells

Cited by 24 publications

References 22 publications

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

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

RGD peptides induce relaxation of pulmonary arteries and airwaysviaβ3‐integrins

The β ₂ agonist terbutaline specifically decreases pulmonary arterial pressure under normoxia and hypoxia via a adrenoceptor antagonism

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Identification of Magnetic Nanoparticles for Combined Positioning and Lentiviral Transduction of Endothelial Cells

Cited by 24 publications

References 22 publications

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

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

RGD peptides induce relaxation of pulmonary arteries and airwaysviaβ3‐integrins

The β 2 agonist terbutaline specifically decreases pulmonary arterial pressure under normoxia and hypoxia via a adrenoceptor antagonism

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The β ₂ agonist terbutaline specifically decreases pulmonary arterial pressure under normoxia and hypoxia via a adrenoceptor antagonism