Magnetisches Drug Targeting—ein neuer Ansatz in der lokoregionären Tumortherapie mit Chemotherapeutika

Alexiou, Christoph; Jurgons, Roland; Schmid, Roswitha J.; Erhardt, W.; Parak, F.; Bergemann, Christian; Iro, Heinrich

doi:10.1007/s00106-004-1146-5

Cited by 52 publications

(24 citation statements)

References 11 publications

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“…[8][9][10] Nevertheless, some of the data on MCM-41 cell-based screens were found to be misleading due to the interference of MCM-41 itself with the 2,5-diphenyltetrazolium salt (MTT) used to asses toxicity. 11,12 Iron oxide NPs (Fe 2 O 3 or Fe 3 O 4 ) have been widely applied as magnetic drug targeting systems 13,14 and contrast agents in magnetic imaging. Cell-based cytotoxicity studies have shown that human mesothelioma cells are sensitive to Fe 2 O 3 -NPs exposure, but rodent 3T3 cells are non-responsive.…”

Section: 7mentioning

confidence: 99%

Evaluation of Toxicity and Gene Expression Changes Triggered by Oxide Nanoparticles

Dua¹,

Chaudhari²,

Lee³

et al. 2011

Bulletin of the Korean Chemical Society

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Several studies have demonstrated that nanoparticles (NPs) have toxic effects on cultured cell lines, yet there are no clear data describing the overall molecular changes induced by NPs currently in use for human applications. In this study, the in vitro cytotoxicity of three oxide NPs of around 100 nm size, namely, mesoporous silica (MCM-41), iron oxide (Fe 2 O 3 -NPs), and zinc oxide (ZnO-NPs), was evaluated in the human embryonic kidney cell line HEK293. Cell viability assays demonstrated that 100 µg/mL MCM-41, 100 µg/mL Fe 2 O 3 , and 12.5 µg/mL ZnO exhibited 20% reductions in HEK293 cell viability in 24 hrs. DNA microarray analysis was performed on cells treated with these oxide NPs and further validated by real time PCR to understand cytotoxic changes occurring at the molecular level. Microarray analysis of NP-treated cells identified a number of up-and down-regulated genes that were found to be associated with inflammation, stress, and the cell death and defense response. At both the cellular and molecular levels, the toxicity was observed in the following order: ZnO-NPs > Fe 2 O 3 -NPs > MCM-41. In conclusion, our study provides important information regarding the toxicity of these three commonly used oxide NPs, which should be useful in future biomedical applications of these nanoparticles.Key Words : MCM-41, Fe 2 O 3 nanoparticle, ZnO nanoparticle, HEK293, Microarray Introduction Nanoparticles (NPs) have increased surface area to weight ratios relative to the same materials in the non-nano size range. In addition to unusual physical properties, NPs are also more chemically reactive than larger particles, which can be either advantageous or harmful depending on their end use. The nanotech boom started around a decade ago and since then the use of NPs in consumer goods and biomedical applications has dramatically increased. NPs are increasingly applied as drug delivery vehicles, biosensors, imaging contrast reagents, and therapeutic agents. However, it is surprising that even today the scientific and industrial community has no sufficiently clear data on the overall effects of these NPs on human health.NPs are easily internalized into cells 1,2 and some NPs have even been shown to cross the blood brain barrier 3-5 where they alter biological processes and cause toxicity. Various in vitro and in vivo studies indicate that some NPs are associated with serious toxicity issues. The most commonly used in vitro toxicity tests focus on whether potentially toxic agents result in cell death. However, sublethal cellular changes may also exist that are not visible in such toxicity screens, but may significantly affect biological processes at the organismal level. Hence, it is important to identify overall cellular changes mediated by NP exposure. Identification of molecular signatures of toxicity at the genomic or proteomic levels provides comprehensive and reliable high throughput data. These data can then be used to compare, classify, and grade a NP on a scale of toxicity. In the present study we identified the m...

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Section: 7mentioning

confidence: 99%

Evaluation of Toxicity and Gene Expression Changes Triggered by Oxide Nanoparticles

Dua¹,

Chaudhari²,

Lee³

et al. 2011

Bulletin of the Korean Chemical Society

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“…The most striking examples have been presented in Alexiou et al (2005) in experiments with rabbits with artifically initiated limb tumours. It is demonstrated that treatments using only 20% of the standard drug amount with an active magnetic targeting showed full recovery of treated limbs.…”

Section: Introductionmentioning

confidence: 99%

Numerical analysis of blood flow in realistic arteries subjected to strong non-uniform magnetic fields

Kenjereš¹

2008

International Journal of Heat and Fluid Flow

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The paper reports on a comprehensive mathematical model for simulations of blood-flow under the presence of strong non-uniform magnetic fields. The model consists of a set of Navier-Stokes equations accounting for the Lorentz and magnetisation forces, and a simplified set of Maxwell's equations (Biot-Savart/Ampere's law) for treating the imposed magnetic fields. The relevant hydrodynamic and electro-magnetic properties of human blood were taken from the literature.The model is then validated for different test cases ranging from a simple cylindrical geometry to real-life right-coronary arteries in humans. The time-dependency of the wall-shear-stress for different stenosis growth rates and the effects of the imposed strong non-uniform magnetic fields on the blood flow pattern are presented and analysed. It is concluded that an imposed nonuniform magnetic field can create significant changes in the secondary flow patterns, thus making it possible to use this technique for optimisations of targeted drug delivery.

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“…Interestingly, one study of nanoparticles loaded with a chemotherapeutic agent has shown reversal of multidrug resistance. 6 At present, Fe 3 O 4 is one of the most commonly used nanoparticle materials, with low toxicity, magnetic properties, and minimal impact on body metabolism. 6,26,29 In order to make the magnetic nanoparticles accumulate locally at the tumor site, an external alternating magnetic field is usually required, as well as magnetic nanoparticles with additional hyperthermia.…”

Section: Discussionmentioning

confidence: 99%

“…6 At present, Fe 3 O 4 is one of the most commonly used nanoparticle materials, with low toxicity, magnetic properties, and minimal impact on body metabolism. 6,26,29 In order to make the magnetic nanoparticles accumulate locally at the tumor site, an external alternating magnetic field is usually required, as well as magnetic nanoparticles with additional hyperthermia. 29 Hyperthermia is an old but nowadays rapidly developing method of treating cancer, whereby a temperature of 40°C-45°C is considered optimal for hyperthermia.…”

Section: Discussionmentioning

confidence: 99%

“…4 Chinese herbal medicine, nanoparticles, and hyperthermia have contributed a lot to this line of research. [5][6][7] It is well known that hyperthermia adjuvant to chemotherapy is playing an increasing role in the treatment of multidrug-resistant tumors in vivo, but temperature has been difficult to control. 7 Fortunately, recent evidence in the literature suggests that magnetic nanoparticles can be used to improve the efficiency of hyperthermia and to regulate temperature at a stable level.…”

Section: Introductionmentioning

confidence: 99%

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Multifunctional magnetic Fe3O4 nanoparticles combined with chemotherapy and hyperthermia to overcome multidrug resistance

Ren¹,

Chen²

2012

IJN

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Background: Multidrug resistance in cancer is a major obstacle for clinical therapeutics, and is the reason for 90% of treatment failures. This study investigated the efficiency of novel multifunctional Fe 3 O 4 magnetic nanoparticles (Fe 3 O 4 -MNP) combined with chemotherapy and hyperthermia for overcoming multidrug resistance in an in vivo model of leukemia. Methods: Nude mice with tumor xenografts were randomly divided into a control group, and the treatment groups were allocated to receive daunorubicin, 5-bromotetrandrine (5-BrTet) and daunorubicin, Fe 3 O 4 -MNP, and Fe 3 O 4 -MNP coloaded with daunorubicin and 5-bromotetrandrine (Fe 3 O 4 -MNP-DNR-5-BrTet), with hyperthermia in an alternating magnetic field. We investigated tumor volume and pathology, as well as P-glycoprotein, Bcl-2, Bax, and caspase-3 protein expression to elucidate the effect of multimodal treatment on overcoming multidrug resistance.

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Magnetisches Drug Targeting—ein neuer Ansatz in der lokoregionären Tumortherapie mit Chemotherapeutika

Abstract: Magnetic Drug Targeting offers an unique opportunity to treat tumors locoregionally with chemotherapeutic agents.

Cited by 52 publications

References 11 publications

Evaluation of Toxicity and Gene Expression Changes Triggered by Oxide Nanoparticles

Evaluation of Toxicity and Gene Expression Changes Triggered by Oxide Nanoparticles

Numerical analysis of blood flow in realistic arteries subjected to strong non-uniform magnetic fields

Multifunctional magnetic Fe3O4 nanoparticles combined with chemotherapy and hyperthermia to overcome multidrug resistance

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