Cancer therapy with drug loaded magnetic nanoparticles—magnetic drug targeting

Alexiou, Christoph; Tietze, Rainer; Schreiber, Eveline; Jurgons, Roland; Richter, Heike; Trahms, Lutz; Rahn, Helene; Odenbach, Stefan; Lyer, Stefan

doi:10.1016/j.jmmm.2010.11.059

Cited by 107 publications

(62 citation statements)

References 13 publications

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“…[1][2][3] In this concept, drug accumulation in the tumor can be achieved with a drug-loaded magnetic carrier system, which is physically directed to the region of interest by an external magnetic field. 4,5 In comparison to conventional drug administration, this leads to an effective increase in the drug concentration in the affected tissue as well as a reduced drug concentration in the rest of the body.…”

Section: Introductionmentioning

confidence: 99%

Hypericin-bearing magnetic iron oxide nanoparticles for selective drug delivery in photodynamic therapy

Unterweger¹,

Subatzus²,

Tietze³

et al. 2015

IJN

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Combining the concept of magnetic drug targeting and photodynamic therapy is a promising approach for the treatment of cancer. A high selectivity as well as significant fewer side effects can be achieved by this method, since the therapeutic treatment only takes place in the area where accumulation of the particles by an external electromagnet and radiation by a laser system overlap. In this article, a novel hypericin-bearing drug delivery system has been developed by synthesis of superparamagnetic iron oxide nanoparticles (SPIONs) with a hypericin-linked functionalized dextran coating. For that, sterically stabilized dextran-coated SPIONs were produced by coprecipitation and crosslinking with epichlorohydrin to enhance stability. Carboxymethylation of the dextran shell provided a functionalized platform for linking hypericin via glutaraldehyde. Particle sizes obtained by dynamic light scattering were in a range of 55–85 nm, whereas investigation of single magnetite or maghemite particle diameter was performed by transmission electron microscopy and X-ray diffraction and resulted in approximately 4.5–5.0 nm. Surface chemistry of those particles was evaluated by Fourier transform infrared spectroscopy and ζ potential measurements, indicating successful functionalization and dispersal stabilization due to a mixture of steric and electrostatic repulsion. Flow cytometry revealed no toxicity of pure nanoparticles as well as hypericin without exposure to light on Jurkat T-cells, whereas the combination of hypericin, alone or loaded on particles, with light-induced cell death in a concentration and exposure time-dependent manner due to the generation of reactive oxygen species. In conclusion, the combination of SPIONs’ targeting abilities with hypericin’s phototoxic properties represents a promising approach for merging magnetic drug targeting with photodynamic therapy for the treatment of cancer.

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Section: Introductionmentioning

confidence: 99%

Hypericin-bearing magnetic iron oxide nanoparticles for selective drug delivery in photodynamic therapy

Unterweger¹,

Subatzus²,

Tietze³

et al. 2015

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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“…Another application that has been pursued is the use of a magnetic field gradient to hold or guide SPIOs to a desired place where they can release the load of molecules. 5,6 Sivakumar et al 7 prepared magnetic nanoparticles, coated with bacterial exopolysaccharides mauran and gellan gums, exhibiting excellent biocompatibility and low cellular cytotoxicity, demonstrating therapeutic potential for application in magnetic hyperthermia, as well as targeted drug delivery, and cancer cell imaging. SPIOs can also be used as thermoseeds capable of absorbing and converting electromagnetic energy, instead of oscillating magnetic fields, into heat warming up their immediate neighborhood.…”

mentioning

confidence: 99%

Ultrasmall cationic superparamagnetic iron oxide nanoparticles as nontoxic and efficient MRI contrast agent and magnetic-targeting tool

Uchiyama¹,

Toma²,

Rodrigues³

et al. 2015

IJN

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Fully dispersible, cationic ultrasmall (7 nm diameter) superparamagnetic iron oxide nanoparticles, exhibiting high relaxivity (178 mM −1 s −1 in 0.47 T) and no acute or subchronic toxicity in Wistar rats, were studied and their suitability as contrast agents for magnetic resonance imaging and material for development of new diagnostic and treatment tools demonstrated. After intravenous injection (10 mg/kg body weight), they circulated throughout the vascular system causing no microhemorrhage or thrombus, neither inflammatory processes at the mesentery vascular bed and hepatic sinusoids (leukocyte rolling, adhesion, or migration as evaluated by intravital microscopy), but having been spontaneously concentrated in the liver, spleen, and kidneys, they caused strong negative contrast. The nanoparticles are cleared from kidneys and bladder in few days, whereas the complete elimination from liver and spleen occurred only after 4 weeks. Ex vivo studies demonstrated that cationic ultrasmall superparamagnetic iron oxide nanoparticles caused no effects on hepatic and renal enzymes dosage as well as on leukocyte count. In addition, they were readily concentrated in rat thigh by a magnet showing its potential as magnetically targeted carriers of therapeutic and diagnostic agents. Summarizing, cationic ultrasmall superparamagnetic iron oxide nanoparticles are nontoxic and efficient magnetic resonance imaging contrast agents useful as platform for the development of new materials for application in theranostics.

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Cancer therapy with drug loaded magnetic nanoparticles—magnetic drug targeting

Cited by 107 publications

References 13 publications

Hypericin-bearing magnetic iron oxide nanoparticles for selective drug delivery in photodynamic therapy

Hypericin-bearing magnetic iron oxide nanoparticles for selective drug delivery in photodynamic therapy

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

Ultrasmall cationic superparamagnetic iron oxide nanoparticles as nontoxic and efficient MRI contrast agent and magnetic-targeting tool

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