Efficient drug-delivery using magnetic nanoparticles — biodistribution and therapeutic effects in tumour bearing rabbits

Tietze, Rainer; Lyer, Stefan; Dürr, Stephan; Struffert, Tobias; Engelhorn, Tobias; Schwarz, Marc; Eckert, Elisabeth; Göen, Thomas; Vasylyev, S.; Peukert, Wolfgang; Wiekhorst, Frank; Trahms, Lutz; Dörfler, Arnd; Alexiou, Christoph

doi:10.1016/j.nano.2013.05.001

Cited by 201 publications

(151 citation statements)

References 36 publications

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“…These were also the reasons why the presence of maghemite cannot be fully excluded. Additionally, the full width at half maximum of the (311) peak can be used to calculate the crystallite size according to the Debye-Scherrer formula (7). The obtained value of d XRD =4.3 nm for SEON DEX 2.0 coincides with the mean core particle size of d TEM =4.6±0.8 nm.…”

mentioning

confidence: 71%

“…[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%

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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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mentioning

confidence: 71%

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

Self Cite

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“…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%

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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“…In this context, a high accumulation of chemotherapeutic drugs (e.g. mitoxantrone) previously bound to nanoparticles could be achieved [36].…”

Section: Challenges Of Accumulation Of the Magnetic Materials At The Tmentioning

confidence: 99%

Means to increase the therapeutic efficiency of magnetic heating of tumors

Kettering

Grau

Pömpner

et al. 2015

Biomedical Engineering / Biomedizinische Technik

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Abstract:The treatment of tumors via hyperthermia has gained increased attention in the last years. Among the different modalities available so far, magnetic hyperthermia has the particular advantage of offering the possibility of depositing the heating source directly into the tumor. In this study, we summarized the present knowledge we gained on how to improve the therapeutic efficiency of magnetic hyperthermia using magnetic nanoparticles (MNPs), with particular consideration of the intratumoral infiltration of the magnetic material. We found that (1) MNPs will be mainly immobilized at the tumor area and that this aspect has to be considered when estimating the heating potential of MNPs, (2) the intratumoral distribution patterns via slow infiltration might well be modulated by specific MNP coating and magnetic targeting, (3) imaging of the nanoparticle depositions within the tumor might allow to correct the distribution pattern via multiple applications, (4) multiple therapeutic sessions are feasible because MNPs are not delivered from the tumor site during the heating process, (5) the utilization of MNPs that internalize into cells will favor the production of intracellular heating spots rather than extracellular ones, (6) utilization of MNPs functionalized with chemotherapeutic agents will allow us to exploit the additive effects of both therapeutic modalities, and (7) distinct cytopathological and histopathological alterations in target tissues are induced as a result of magnetic hyperthermia. However, the accumulation at the tumor via intravenous application remains a matter of challenge.

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Efficient drug-delivery using magnetic nanoparticles — biodistribution and therapeutic effects in tumour bearing rabbits

Cited by 201 publications

References 36 publications

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

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

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

Means to increase the therapeutic efficiency of magnetic heating of tumors

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