Optimization of Magnetic Nanoparticle-Assisted Lentiviral Gene Transfer

Trueck, Christina; Zimmermann, Katrin; Mykhaylyk, Olga; Anton, Martina; Vosen, Sarah; Wenzel, Daniela; Fleischmann, Bernd K.; Pfeifer, Alexander

doi:10.1007/s11095-011-0660-x

Cited by 26 publications

(25 citation statements)

References 37 publications

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“…For this purpose different types of MNPs have been developed in recent years which have properties like low toxicity, adequate circulation times or controllable magnetic responsiveness [8]. Most previous studies focussed on their implementation in tumour treatment [9] while another application under research is the transport of genetic material or stem cells via MNP-incorporation [10,11]. …”

Section: Introductionmentioning

confidence: 99%

Increased accumulation of magnetic nanoparticles by magnetizable implant materials for the treatment of implant-associated complications

Angrisani

Foth

Kietzmann

et al. 2013

Journal of Nanobiotechnology

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BackgroundIn orthopaedic surgery, accumulation of agents such as anti-infectives in the bone as target tissue is difficult. The use of magnetic nanoparticles (MNPs) as carriers principally enables their accumulation via an externally applied magnetic field. Magnetizable implants are principally able to increase the strength of an externally applied magnetic field to reach also deep-seated parts in the body. Therefore, the integration of bone-addressed therapeutics in MNPs and their accumulation at a magnetic orthopaedic implant could improve the treatment of implant related infections. In this study a martensitic steel platelet as implant placeholder was used to examine its accumulation and retention capacity of MNPs in an in vitro experimental set up considering different experimental frame conditions as magnet quantity and distance to each other, implant thickness and flow velocity.ResultsThe magnetic field strength increased to approximately 112% when a martensitic stainless steel platelet was located between the magnet poles. Therewith a significantly higher amount of magnetic nanoparticles could be accumulated in the area of the platelet compared to the sole magnetic field. During flushing of the tube system mimicking the in vivo blood flow, the magnetized platelet was able to retain a higher amount of MNPs without an external magnetic field compared to the set up with no mounted platelet during flushing of the system. Generally, a higher flow velocity led to lower amounts of accumulated MNPs. A higher quantity of magnets and a lower distance between magnets led to a higher magnetic field strength. Albeit not significantly the magnetic field strength tended to increase with thicker platelets.ConclusionA martensitic steel platelet significantly improved the attachment of magnetic nanoparticles in an in vitro flow system and therewith indicates the potential of magnetic implant materials in orthopaedic surgery. The use of a remanent magnetic implant material could improve the efficiency of capturing MNPs especially when the external magnetic field is turned off thus facilitating and prolonging the effect. In this way higher drug levels in the target area might be attained resulting in lower inconveniences for the patient.

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Section: Introductionmentioning

confidence: 99%

Increased accumulation of magnetic nanoparticles by magnetizable implant materials for the treatment of implant-associated complications

Angrisani

Foth

Kietzmann

et al. 2013

Journal of Nanobiotechnology

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“…The use of MNP in combination with various genetic vectors (magnetofection method) has been object of several in vitro and in vivo studies by us 7, 8, 22, 23 and other groups 15, 24, 25. However, gene targeting by MNP, especially after systemic administration in vivo , has proven to be insufficient probably due to low magnetic moments of the single MNP, particle aggregation in the blood, and rapid clearance from the circulation.…”

Section: Discussionmentioning

confidence: 99%

“…Non integrating fluorescent labeled lentiviral particles pCHIV.eGFP were generated as described by Lampe et al40. The physical viral titers (viral particles, VP) of lentiviral preparations were determined by reverse transcriptase activity measurements25 and biological titers (infectious particles) were determined by transduction of HEK293T cells and flow cytometry of transduced cells as described elsewhere39.…”

Section: Methodsmentioning

confidence: 99%

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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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“…Magnetofection has been used in the field of respiratory epithelial cells to increase nonviral-mediated gene transfer [18,19,20,21] and to study the mechanism of internalization [22]. Although many studies have demonstrated that by using viral magnetofection systems, the expression of a transgene is often significantly higher in comparison to only inoculating with virus alone in many cell types [23,24,25,26,27], our previous work was the first to show that LV-mediated transduction of bronchial epithelial cells is enhanced by magnetofection [13]. Moreover, only a few studies have demonstrated the usefulness of magnetofection in targeting applications that require penetration of a cellular or a tessutal barrier [28].…”

Section: Discussionmentioning

confidence: 99%

Magnetofection Enhances Lentiviral-Mediated Transduction of Airway Epithelial Cells through Extracellular and Cellular Barriers

Castellani

Orlando

Carbone

et al. 2016

Genes

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Gene transfer to airway epithelial cells is hampered by extracellular (mainly mucus) and cellular (tight junctions) barriers. Magnetofection has been used to increase retention time of lentiviral vectors (LV) on the cellular surface. In this study, magnetofection was investigated in airway epithelial cell models mimicking extracellular and cellular barriers. Bronchiolar epithelial cells (H441 line) were evaluated for LV-mediated transduction after polarization onto filters and dexamethasone (dex) treatment, which induced hemicyst formation, with or without magnetofection. Sputum from cystic fibrosis (CF) patients was overlaid onto cells, and LV-mediated transduction was evaluated in the absence or presence of magnetofection. Magnetofection of unpolarized H441 cells increased the transduction with 50 MOI (multiplicity of infection, i.e., transducing units/cell) up to the transduction obtained with 500 MOI in the absence of magnetofection. Magnetofection well-enhanced LV-mediated transduction in mucus-layered cells by 20.3-fold. LV-mediated transduction efficiency decreased in dex-induced hemicysts in a time-dependent fashion. In dome-forming cells, zonula occludens-1 (ZO-1) localization at the cell borders was increased by dex treatment. Under these experimental conditions, magnetofection significantly increased LV transduction by 5.3-fold. In conclusion, these results show that magnetofection can enhance LV-mediated gene transfer into airway epithelial cells in the presence of extracellular (sputum) and cellular (tight junctions) barriers, representing CF-like conditions.

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Optimization of Magnetic Nanoparticle-Assisted Lentiviral Gene Transfer

Abstract: MNP-guided lentiviral transduction of endothelial cells can be significantly enhanced and localized by using optimized MNPs.

Cited by 26 publications

References 37 publications

Increased accumulation of magnetic nanoparticles by magnetizable implant materials for the treatment of implant-associated complications

Increased accumulation of magnetic nanoparticles by magnetizable implant materials for the treatment of implant-associated complications

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

Magnetofection Enhances Lentiviral-Mediated Transduction of Airway Epithelial Cells through Extracellular and Cellular Barriers

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