Magnetic Drug Targeting Reduces the Chemotherapeutic Burden on Circulating Leukocytes

Janko, Christina; Dürr, Stephan; Muñoz, Luis; Lyer, Stefan; Chaurio, Ricardo A.; Tietze, Rainer; Löhneysen, Sarah von; Schorn, Christine; Herrmann, Martin; Alexiou, Christoph

doi:10.3390/ijms14047341

Cited by 55 publications

(38 citation statements)

References 27 publications

(30 reference statements)

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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%

“…Experiments were performed in triplicates within each of the three independent experiments. Product amplification was measured via the LightCycler ® 480 SYBR Green I Master (Roche, Germany) and the Mastercycler ® ep realplex 4 S device (Eppendorf AG, Hamburg, Germany). The purity of amplified products was verified by melting curve analysis.…”

Section: Mrna Expression Of Selected Genes Involved In Mtx Metabolizamentioning

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: Mrna Expression Of Selected Genes Involved In Mtx Metabolizamentioning

confidence: 99%

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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“…[1][2][3] Its basic principle is to physically direct a loaded magnetic drug carrier system to a specific organ or tissue with an externally applied magnetic field for drug accumulation. 4,5 Compared with conventional drug administration, this strategy leads, on the one hand, to a reduced drug concentration in the body compartments overall, thus decreasing systemic side effects, including nausea, hair loss, and neurotoxicity; [6][7][8] on the other hand, the concentration in the affected tissue is effectively increased, resulting in an enhanced therapeutic effect.…”

Section: Introductionmentioning

confidence: 99%

Development and characterization of magnetic iron oxide nanoparticles with a cisplatin-bearing polymer coating for targeted drug delivery

Unterweger¹,

Tietze²,

Janko³

et al. 2014

IJN

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A highly selective and efficient cancer therapy can be achieved using magnetically directed superparamagnetic iron oxide nanoparticles (SPIONs) bearing a sufficient amount of the therapeutic agent. In this project, SPIONs with a dextran and cisplatin-bearing hyaluronic acid coating were successfully synthesized as a novel cisplatin drug delivery system. Transmission electron microscopy images as well as X-ray diffraction analysis showed that the individual magnetite particles were around 4.5 nm in size and monocrystalline. The small crystallite sizes led to the superparamagnetic behavior of the particles, which was exemplified in their magnetization curves, acquired using superconducting quantum interference device measurements. Hyaluronic acid was bound to the initially dextran-coated SPIONs by esterification. The resulting amide bond linkage was verified using Fourier transform infrared spectroscopy. The additional polymer layer increased the vehicle size from 22 nm to 56 nm, with a hyaluronic acid to dextran to magnetite weight ratio of 51:29:20. A maximum payload of 330 μg cisplatin/mL nanoparticle suspension was achieved, thus the particle size was further increased to around 77 nm with a zeta potential of −45 mV. No signs of particle precipitation were observed over a period of at least 8 weeks. Analysis of drug-release kinetics using the dialysis tube method revealed that these were driven by inverse ligand substitution and diffusion through the polymer shell as well as enzymatic degradation of hyaluronic acid. The biological activity of the particles was investigated in a nonadherent Jurkat cell line using flow cytometry. Further, cell viability and proliferation was examined in an adherent PC-3 cell line using xCELLigence analysis. Both tests demonstrated that particles without cisplatin were biocompatible with these cells, whereas particles with the drug induced apoptosis in a dose-dependent manner, with secondary necrosis after prolonged incubation. In conclusion, combination of dextran-coated SPIONs with hyaluronic acid and cisplatin represents a promising approach for magnetic drug targeting in the treatment of cancer.

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“…Using SPIONs, hyperthermia of tumor-accumulated particles in the presence of an external alternating magnetic field or magnetic drug targeting (MDT) after SPION conjugation with chemotherapeutic drugs has been reported. 8,[12][13][14][15][16][17] Additionally, by combining imaging and therapy, SPIONs have the potential to serve as theranostics. 18 Despite numerous published research papers describing promising nanoparticles for medical applications, only very few nanoparticle types have been translated into the clinics to date.…”

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confidence: 99%

Selection of potential iron oxide nanoparticles for breast cancer treatment based on in vitro cytotoxicity and cellular uptake

Poller¹,

Zaloga²,

Schreiber³

et al. 2017

IJN

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Superparamagnetic iron oxide nanoparticles (SPIONs) are promising tools for the treatment of different diseases. Their magnetic properties enable therapies involving magnetic drug targeting (MDT), hyperthermia or imaging. Depending on the intended treatment, specific characteristics of SPIONs are required. While particles used for imaging should circulate for extended periods of time in the vascular system, SPIONs intended for MDT or hyperthermia should be accumulated in the target area to come into close proximity of, or to be incorporated into, specific tumor cells. In this study, we determined the impact of several accurately characterized SPION types varying in size, zeta potential and surface coating on various human breast cancer cell lines and endothelial cells to identify the most suitable particle for future breast cancer therapy. We analyzed cellular SPION uptake, magnetic properties, cell proliferation and toxicity using atomic emission spectroscopy, magnetic susceptometry, flow cytometry and microscopy. The results demonstrated that treatment with dextran-coated SPIONs (SPION Dex ) and lauric acid-coated SPIONs (SPION LA ) with an additional protein corona formed by human serum albumin (SPION LA-HSA ) resulted in very moderate particle uptake and low cytotoxicity, whereas SPION LA had in part much stronger effects on cellular uptake and cellular toxicity. In summary, our data show significant dose-dependent and particle type-related response differences between various breast cancer and endothelial cells, indicating the utility of these particle types for distinct medical applications.

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Magnetic Drug Targeting Reduces the Chemotherapeutic Burden on Circulating Leukocytes

Cited by 55 publications

References 27 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

Development and characterization of magnetic iron oxide nanoparticles with a cisplatin-bearing polymer coating for targeted drug delivery

Selection of potential iron oxide nanoparticles for breast cancer treatment based on in vitro cytotoxicity and cellular uptake

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