Magnetic Targeting of Magnetoliposomes to Solid Tumors with MR Imaging Monitoring in Mice: Feasibility

Fortin-Ripoche, Jean-Paul; Martina, Marie Sophie; Gazeau, Florence; Ménager, Christine; Wilhelm, Claire; Bacri, Jean‐Claude; Lesieur, Sylviane; Clémеnt, Olivier

doi:10.1148/radiol.2392042110

Cited by 141 publications

(95 citation statements)

References 43 publications

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“…Furthermore, MTX-MNP also offer the possibility of magnetic targeting, allowing the "guidance" of MTX-MNP to the tumor region by magnetic forces and, hence, facilitating a localized accumulation of MTX-MNP in the tumor region. [3][4][5][6][7] In this regard, the low release of MTX from the MTX-MNP will additionally lead to a reduction of systemic side effects during the targeting process.…”

Section: International Journal Of Nanomedicine Downloaded From Httpsmentioning

confidence: 99%

“…Hereto, MNP will be able to deposit their cargo (eg, a coupled chemotherapeutic drug) at the target site whereby unwanted side effects can be reduced. [3][4][5][6][7] Moreover, MNP can be heated in an alternating magnetic field, allowing a localized sensitization or destruction of tumor cells or tumor tissue by hyperthermal or even thermoablative temperatures. [8][9][10][11] For magnetic heating purposes, iron oxide MNP with a clustered magnetite or maghemite core and an appropriate coating (polyethylene glycol [PEG], dextran, dimercaptosuccinic acid [DMSA], etc) have been shown to exhibit good heating capabilities and biocompatibility.…”

Section: Introductionmentioning

confidence: 99%

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Heterogeneous response of different tumor cell lines to methotrexate-coupled nanoparticles in presence of hyperthermia

Stapf¹,

Pömpner²,

Teichgräber³

et al. 2016

IJN

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Today, the therapeutic efficacy of cancer is restricted by the heterogeneity of the response of tumor cells to chemotherapeutic drugs. Since those therapies are also associated with severe side effects in nontarget organs, the application of drugs in combination with nanocarriers for targeted therapy has been suggested. Here, we sought to assess whether the coupling of methotrexate (MTX) to magnetic nanoparticles (MNP) could serve as a valuable tool to circumvent the heterogeneity of tumor cell response to MTX by the combined treatment with hyperthermia. To this end, we investigated five breast cancer cell lines of different origin and with different mutational statuses, as well as a bladder cancer cell line in terms of their response to exposure to MTX as a free drug or after its coupling to MNP as well as in presence/absence of hyperthermia. We also assessed whether the effects could be connected to the cell line-specific expression of proteins related to the uptake and efflux of MTX and MNP. Our results revealed a very heterogeneous and cell line-dependent response to an exposure with MTX-coupled MNP (MTX–MNP), which was almost comparable to the efficacy of free MTX in the same cell line. Moreover, a cell line-specific and preferential uptake of MTX–MNP compared with MNP alone was found (probably by receptor-mediated endocytosis), agreeing with the observed cytotoxic effects. Opposed to this, the expression pattern of several cell membrane transport proteins noted for MTX uptake and efflux was only by tendency in agreement with the cellular toxicity of MTX–MNP in different cell lines. Higher cytotoxic effects were achieved by exposing cells to a combination of MTX–MNP and hyperthermal treatment, compared with MTX or thermo-therapy alone. However, the heterogeneity in the response of the tumor cell lines to MTX could not be completely abolished – even after its combination with MNP and/or hyperthermia – and the application of higher thermal dosages might be necessary.

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Section: International Journal Of Nanomedicine Downloaded From Httpsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Heterogeneous response of different tumor cell lines to methotrexate-coupled nanoparticles in presence of hyperthermia

Stapf¹,

Pömpner²,

Teichgräber³

et al. 2016

IJN

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“…It should also be noted that the magnitude of applications, such as magnetic vectorization. We have previously succeeded in guiding synthetic magnetic vechoming may also have been reduced by the relatively small number of cells, a decision dictated by their large tors such as magnetoliposomes to tumor sites (13) and to the cerebral microcirculation (34). Other recent studsize (13 µm) and the resulting risk of coronary thrombosis.…”

Section: Magnetic Labeling Of Epcsmentioning

confidence: 99%

Can Magnetic Targeting of Magnetically Labeled Circulating Cells Optimize Intramyocardial Cell Retention?

et al. 2012

Self Cite

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Therapeutic intracavitary stem cell infusion currently suffers from poor myocardial homing. We examined whether cardiac cell retention could be enhanced by magnetic targeting of endothelial progenitor cells (EPCs) loaded with iron oxide nanoparticles. EPCs were magnetically labeled with citrate-coated iron oxide nanoparticles. Cell proliferation, migration, and CXCR4 chemokine receptor expression were assessed in different labeling conditions and no adverse effects of the magnetic label were observed. The magnetophoretic mobility of labeled EPCs was determined in vitro, with the same magnet as that subsequently used in vivo. Coronary artery occlusion was induced for 30 min in 36 rats (31 survivors), followed by 20 min of reperfusion. The rats were randomized to receive, during brief aortic cross-clamping, direct intraventricular injection of culture medium (n = 7) or magnetically labeled EPCs (n = 24), with (n = 14) or without (n = 10) subcutaneous insertion of a magnet over the chest cavity (n = 14). The hearts were explanted 24 h later and engrafted cells were visualized by magnetic resonance imaging (MRI) of the heart at 1.5 T. Their abundance in the myocardium was also analyzed semiquantitatively by immunofluorescence, and quantitatively by real-time polymerase chain reaction (RT-PCR).Although differences in cell retention between groups failed to be statistically significant using RT-PCR quantification, due to the variability of the animal model, immunostaining showed that the average number of engrafted EPCs was significantly ten times higher with than without magnetic targeting. There was thus a consistent trend favoring the magnet-treated hearts, thereby suggesting magnetic targeting as a potentially new mean of enhancing myocardial homing of intravascularly delivered stem cells. Magnetic targeting has the potential to enhance myocardial retention of intravascularly delivered endothelial progenitor cells.

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“…Principally, research is concentrated on controlling the release of an encapsulated drug. However, their utility as MRI contrast agents has been presented on several occasions (39,52,55). Other applications, such as cell sorting and gene delivery, have also been addressed (64).…”

Section: Magnetoliposomes and The State Of The Artmentioning

confidence: 99%

Magnetoliposomes: opportunities and challenges

Monnier

Burnand

Rothen‐Rutishauser

et al. 2014

European Journal of Nanomedicine

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Combining liposomes with magnetic nanoparticles is an intriguing approach to create multifunctional vesicles for medical applications, which range from controlled drug delivery vehicles to diagnostic imaging enhancers. Over the past decade, significant effort has been invested in developing such hybrids -widely known as magnetoliposomes -and has led to numerous new concepts. This review provides an overview on of the current state of the art in this field. The concept of magnetic fluid hyperthermia and stimuli-responsive nanoparticles for drug delivery is briefly recapitulated. The materials needed for these hybrids are addressed as well. The three typically followed approaches to associate magnetic nanoparticles to the liposomes are described and discussed more in detail. The final chapters are dedicated to the analytical methods used to characterize these hybrids and to theoretical considerations relevant for bilayer-embedded nanoparticles.

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Magnetic Targeting of Magnetoliposomes to Solid Tumors with MR Imaging Monitoring in Mice: Feasibility

Abstract: Magnetic targeting of sterically stabilized magnetoliposomes after they are intravenously injected is feasible in vivo.

Cited by 141 publications

References 43 publications

Heterogeneous response of different tumor cell lines to methotrexate-coupled nanoparticles in presence of hyperthermia

Heterogeneous response of different tumor cell lines to methotrexate-coupled nanoparticles in presence of hyperthermia

Can Magnetic Targeting of Magnetically Labeled Circulating Cells Optimize Intramyocardial Cell Retention?

Magnetoliposomes: opportunities and challenges

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