Dataset Information

Drug delivery to atherosclerotic plaques using superparamagnetic iron oxide nanoparticles.

ABSTRACT:

Introduction

Magnetic drug targeting utilizes superparamagnetic iron oxide nanoparticles (SPIONs) to accumulate drugs in specified vasculature regions.

Methods

We produced SPIONs conjugated with dexamethasone phosphate (SPION-DEXA). The efficacy of magnetic drug targeting was investigated in a rabbit model of atherosclerosis induced by balloon injury and high cholesterol diet.

Results

In vitro, SPION-DEXA were well-tolerated by endothelial cells. SPION-DEXA were internalized by human peripheral blood mononuclear cells and induced CD163 expression comparable with the free drug. In vivo, magnetic targeting of SPIONs to abdominal aorta was confirmed by histology. Upon vascular injury followed by high-cholesterol diet, early administration of SPION-DEXA enhanced the inflammatory burden in the plaques. Increased macrophage content and larger intima- media thickness were observed in animals treated with SPION-DEXA compared with controls. In advanced atherosclerosis, no beneficial effect of local glucocorticoid therapy was detectable.

Conclusion

Magnetic drug targeting represents an efficient platform to deliver drugs to diseased arteries in vivo. However, targeting of vascular injury in the lipid-rich environment using dexamethasone-conjugated SPIONs may cause accelerated inflammatory response.

SUBMITTER: Matuszak J

PROVIDER: S-EPMC6294059 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Drug delivery to atherosclerotic plaques using superparamagnetic iron oxide nanoparticles.

Matuszak Jasmin J Lutz Barbara B Sekita Aleksander A Zaloga Jan J Alexiou Christoph C Lyer Stefan S Cicha Iwona I

International journal of nanomedicine 20181211

<h4>Introduction</h4>Magnetic drug targeting utilizes superparamagnetic iron oxide nanoparticles (SPIONs) to accumulate drugs in specified vasculature regions.<h4>Methods</h4>We produced SPIONs conjugated with dexamethasone phosphate (SPION-DEXA). The efficacy of magnetic drug targeting was investigated in a rabbit model of atherosclerosis induced by balloon injury and high cholesterol diet.<h4>Results</h4>In vitro, SPION-DEXA were well-tolerated by endothelial cells. SPION-DEXA were internalize ...[more]

PMID: 30587970

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Project description:BackgroundOptical coherence tomography (OCT) is an intravascular, high-resolution imaging technique that is used to characterize atherosclerotic plaques. However, the identification of macrophages as important markers of inflammation and plaque vulnerability remains difficult. Here, we investigate whether the uptake of very small iron oxide particles (VSOP) in macrophages, that cluster in phagolysosomes and allow high-quality magnetic resonance imaging (MRI) of atherosclerotic plaques, and uptake of ferumoxytol nanoparticles enhance detection of macrophages by OCT.Materials and methodsRAW 264.7 macrophage cells were incubated with VSOP (1 and 2 mM Fe) that have been clinically tested and ferumoxytol (8.9 mM Fe) that is approved for iron deficiency treatment and currently investigated as an MRI contrast agent. The light scattering of control macrophages, nanoparticle-labeled macrophages (2,000,000 in 500 µL) and nanoparticle suspensions was measured in synchronous wavelength scan mode using a fluorescence spectrophotometer. For OCT analyses, pellets of 8,000,000 non-labeled, VSOP-labeled and ferumoxytol-labeled RAW 264.7 macrophages were imaged and analyzed on an OPTIS™ OCT imaging system.ResultsIncubation with 1 and 2 mM VSOP resulted in uptake of 7.1±1.5 and 12±1.5 pg Fe per cell, which increased the backscattering of the macrophages in spectrophotometry 2.5- and 3.6-fold, whereas incubation with 8.9 mM Fe ferumoxytol resulted in uptake of 6.6±2 pg Fe per cell, which increased the backscattering 1.5-fold at 700 nm. In contrast, backscattering of non-clustered nanoparticles in suspension was negligible. Accordingly, OCT imaging could visualize significantly increased backscattering and signal attenuation of nanoparticle-labeled macrophages in comparison with controls.ConclusionWe conclude that VSOP and, to a lesser extent, ferumoxytol increase light scattering and attenuation when taken up by macrophages and can serve as a multimodal imaging probe for MRI and OCT to improve macrophage detection in atherosclerotic plaques by OCT in the future.

Dataset Information

Drug delivery to atherosclerotic plaques using superparamagnetic iron oxide nanoparticles.

Introduction

Methods

Results

Conclusion

Publications

Drug delivery to atherosclerotic plaques using superparamagnetic iron oxide nanoparticles.

Similar Datasets

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