Neoadjuvant gene delivery of feline granulocyte‐macrophage colony‐stimulating factor using magnetofection for the treatment of feline fibrosarcomas: a phase I trial

Hüttinger, Cornelia; Hirschberger, Johannes; Jahnke, Anika; Köstlin, R; Brill, T.; Plank, Christian; Küchenhoff, Helmut; Krieger, Stefan H.; Schillinger, Ulrike

doi:10.1002/jgm.1185

Cited by 55 publications

(32 citation statements)

References 43 publications

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“…Only three other research groups had used magnetofection for the treatment of tumors in vivo, and demonstrated its efficiency, safety and potential use for the delivery of therapeutic genes. 11,46,47,48,49 However, only in two studies was antitumor effect of magnetofection with therapeutic genes demonstrated. In the first study magnetofection was investigated in combination with RNAi, similar to our study.…”

Section: Discussionmentioning

confidence: 99%

Mcam Silencing With RNA Interference Using Magnetofection has Antitumor Effect in Murine Melanoma

Prosen

Markelc

Dolinšek

et al. 2014

Molecular Therapy - Nucleic Acids

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The melanoma cell adhesion molecule (MCAM) is involved in melanoma development and its progression, including invasiveness, metastatic potential and angiogenesis. Therefore, MCAM represents a potential target for gene therapy of melanoma, whose expression could be hindered with posttranscriptional specific gene silencing with RNA interference technology. In this study, we constructed a plasmid DNA encoding short hairpin RNA against MCAM (pMCAM) to explore the antitumor and antiangiogenic effects. The experiments were performed in vitro on murine melanoma and endothelial cells, as well as in vivo on melanoma tumors in mice. The antiproliferative, antimigratory, antiangiogenic and antitumor effects were examined after gene therapy with pMCAM. Gene delivery was performed by magnetofection, and its efficacy compared to gene electrotransfer. Gene therapy with pMCAM has proved to be an effective approach in reducing the proliferation and migration of melanoma cells, as well as having antiangiogenic effect in endothelial cells and antitumor effect on melanoma tumors. Magnetofection as a developing nonviral gene delivery system was effective in the transfection of melanoma cells and tumors with pMCAM, but less efficient than gene electrotransfer in in vivo tumor gene therapy due to the lack of antiangiogenic effect after silencing Mcam by magnetofection.

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Section: Discussionmentioning

confidence: 99%

Mcam Silencing With RNA Interference Using Magnetofection has Antitumor Effect in Murine Melanoma

Prosen

Markelc

Dolinšek

et al. 2014

Molecular Therapy - Nucleic Acids

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“…The treatment was well-tolerated by most of the animals [49]. In a follow up phase I trial, preoperative felGM-CSF gene therapy had favorable results as assessed by the rate of recurrence in treated versus (surgery-only) control cats [50]. More recently, Tresilwised et al [7] examined the potential of boosting the efficacy of the oncolytic adenovirus dl520 by associating it with MNP and performing magnetic field-guided infection in multidrug-resistant cancer cell cultures and in a murine xenograft model.…”

Section: Therapeutic Potential Of Magnetic Gene Targeting In Vivo Cancermentioning

confidence: 92%

Magnetic Field-Assisted Gene Delivery: Achievements and Therapeutic Potential

Schwerdt

Goya²,

Calatayud³

et al. 2012

CGT

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The discovery in the early 2000's that magnetic nanoparticles (MNPs) complexed to nonviral or viral vectors can, in the presence of an external magnetic field, greatly enhance gene transfer into cells has raised much interest. This technique, called magnetofection, was initially developed mainly to improve gene transfer in cell cultures, a simpler and more easily controllable scenario than in vivo models. These studies provided evidence for some unique capabilities of magnetofection. Progressively, the interest in magnetofection expanded to its application in animal models and led to the association of this technique with another technology, magnetic drug targeting (MDT). This combination offers the possibility to develop more efficient and less invasive gene therapy strategies for a number of major pathologies like cancer, neurodegeneration and myocardial infarction. The goal of MDT is to concentrate MNPs functionalized with therapeutic drugs, in target areas of the body by means of properly focused external magnetic fields. The availability of stable, nontoxic MNP-gene vector complexes now offers the opportunity to develop magnetic gene targeting (MGT), a variant of MDT in which the gene coding for a therapeutic molecule, rather than the molecule itself, is delivered to a therapeutic target area in the body. This article will first outline the principle of magnetofection, subsequently describing the properties of the magnetic fields and MNPs used in this technique. Next, it will review the results achieved by magnetofection in cell cultures. Last, the potential of MGT for implementing minimally invasive gene therapy will be discussed.

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“…In addition, magnetofection contributed to site-specific delivery of antisense oligonucleotides as well as reporter genes attached to SPIONs in vivo (Krötz et al 2003a; Scherer et al 2002). Recently, two trials consisting of dose-escalation neoadjuvant gene therapy to surgery were performed in feline fibrosarcomas in which therapeutic genes were applied by magnetofection (Hüttinger et al 2008; Jahnke et al 2007). The use of SPIONs either as a drug or gene delivery system contributes to the effectiveness of the therapy in many ways.…”

Section: Introductionmentioning

confidence: 99%

Increased Cellular Uptake of Biocompatible Superparamagnetic Iron Oxide Nanoparticles into Malignant Cells by an External Magnetic Field

et al. 2010

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Superparamagnetic iron oxide nanoparticles (SPIONs) are used as delivery systems for different therapeutics including nucleic acids for magnetofection-mediated gene therapy. The aim of our study was to evaluate physicochemical properties, biocompatibility, cellular uptake and trafficking pathways of the custom-synthesized SPIONs for their potential use in magnetofection. Custom-synthesized SPIONs were tested for size, shape, crystalline composition and magnetic behavior using a transmission electron microscope, X-ray diffractometer and magnetometer. SPIONs were dispersed in different aqueous media to obtain ferrofluids, which were tested for pH and stability using a pH meter and zetameter. Cytotoxicity was determined using the MTS and clonogenic assays. Cellular uptake and trafficking pathways were qualitatively evaluated by transmission electron microscopy and quantitatively by inductively coupled plasma atomic emission spectrometry. SPIONs were composed of an iron oxide core with a diameter of 8–9 nm, coated with a 2-nm-thick layer of silica. SPIONs, dispersed in 0.9% NaCl solution, resulted in a stable ferrofluid at physiological pH for several months. SPIONs were not cytotoxic in a broad range of concentrations and were readily internalized into different cells by endocytosis. Exposure to neodymium-iron-boron magnets significantly increased the cellular uptake of SPIONs, predominantly into malignant cells. The prepared SPIONs displayed adequate physicochemical and biomedical properties for potential use in magnetofection. Their cellular uptake was dependent on the cell type, and their accumulation within the cells was dependent on the duration of exposure to an external magnetic field.

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Neoadjuvant gene delivery of feline granulocyte‐macrophage colony‐stimulating factor using magnetofection for the treatment of feline fibrosarcomas: a phase I trial

Cited by 55 publications

References 43 publications

Mcam Silencing With RNA Interference Using Magnetofection has Antitumor Effect in Murine Melanoma

Mcam Silencing With RNA Interference Using Magnetofection has Antitumor Effect in Murine Melanoma

Magnetic Field-Assisted Gene Delivery: Achievements and Therapeutic Potential

Increased Cellular Uptake of Biocompatible Superparamagnetic Iron Oxide Nanoparticles into Malignant Cells by an External Magnetic Field

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