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Decreased reticuloendothelial system clearance and increased blood half-life and immune cell labeling for nano- and micron-sized superparamagnetic iron-oxide particles upon pre-treatment with Intralipid.

ABSTRACT: Superparamagnetic iron-oxide nanoparticles are useful as contrast agents for anatomical, functional and cellular MRI, drug delivery agents, and diagnostic biosensors. Nanoparticles are generally cleared by the reticuloendothelial system (RES), in particular taken up by Kupffer cells in the liver, limiting particle bioavailability and in-vivo applications. Strategies that decrease the RES clearance and prolong the circulation residence time of particles can improve the in-vivo targeting efficiency.Intralipid 20.0%, an FDA approved nutritional supplement, was intravenously administered in rats at the clinical dose (2g/kg) 1h before intravenous injection of ultra-small superparamagnetic iron-oxide (USPIO) or micron-sized paramagnetic iron-oxide (MPIO) particles. Blood half-life, monocyte labeling efficiency, and particle biodistribution were assessed by magnetic resonance relaxometry, flow cytometry, inductively-coupled plasma MS, and histology.Pre-treatment with Intralipid resulted in a 3.1-fold increase in USPIO blood half-life and a 2-fold increase in USPIO-labeled monocytes. A 2.5-fold increase in MPIO blood half-life and a 5-fold increase in MPIO-labeled monocytes were observed following Intralipid pre-treatment, with a 3.2-fold increase in mean iron content up to 2.60pg Fe/monocyte. With Intralipid, there was a 49.2% and 45.1% reduction in liver uptake vs. untreated controls at 48h for USPIO and MPIO, respectively.Intralipid pre-treatment significantly decreases initial RES uptake and increases in-vivo circulation and blood monocyte labeling efficiency for nano- and micron-sized superparamagnetic iron-oxide particles.Our findings can have broad applications for imaging and drug delivery applications, increasing the bioavailability of nano- and micron-sized particles for target sites other than the liver.

SUBMITTER: Liu L

PROVIDER: S-EPMC3640706 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Decreased reticuloendothelial system clearance and increased blood half-life and immune cell labeling for nano- and micron-sized superparamagnetic iron-oxide particles upon pre-treatment with Intralipid.

Liu Li L Hitchens T Kevin TK Ye Qing Q Wu Yijen Y Barbe Brent B Prior Devin E DE Li Wendy F WF Yeh Fang-Cheng FC Foley Lesley M LM Bain Daniel J DJ Ho Chien C

Biochimica et biophysica acta 20130208 6

<h4>Background</h4>Superparamagnetic iron-oxide nanoparticles are useful as contrast agents for anatomical, functional and cellular MRI, drug delivery agents, and diagnostic biosensors. Nanoparticles are generally cleared by the reticuloendothelial system (RES), in particular taken up by Kupffer cells in the liver, limiting particle bioavailability and in-vivo applications. Strategies that decrease the RES clearance and prolong the circulation residence time of particles can improve the in-vivo ...[more]

PMID: 23396002

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Project description:BackgroundThe characteristics of coal dust (CD) particles affect the inhalation of CD, which causes coal worker's pneumoconiosis (CWP). CD nanoparticles (CD-NPs, < 500 nm) and micron particles (CD-MPs, < 5 μm) are components of the respirable CD. However, the differences in physicochemical properties and pulmonary toxicity between CD-NPs and CD-MPs remain unclear.MethodsCD was analyzed by scanning electron microscopy, Malvern nanoparticle size potentiometer, energy dispersive spectroscopy, infrared spectroscopy, and electron paramagnetic resonance spectroscopy. CCK-8 assay, ELISA, transmission electron microscope, JC-1 staining, reactive oxygen species activity probe, calcium ion fluorescent probe, AO/EB staining, flow cytometry, and western blot were used to determine the differences between CD-NPs and CD-MPs on acute pulmonary toxicity. CCK-8, scratch healing and Transwell assay, hematoxylin-eosin and Masson staining, immunohistochemistry, immunofluorescence, and western blot were applied to examine the effects of CD-NPs and CD-MPs on pneumoconiosis.ResultsAnalysis of the size distribution of CD revealed that the samples had been size segregated. The carbon content of CD-NPs was greater than that of CD-MPs, and the oxygen, aluminum, and silicon contents were less. In in vitro experiments with A549 and BEAS-2B cells, CD-NPs, compared with CD-MPs, had more inflammatory vacuoles, release of pro-inflammatory cytokines (IL-6, IL-1β, TNFα) and profibrotic cytokines (CXCL2, TGFβ1), mitochondrial damage (reactive oxygen species and Ca2+ levels and decreased mitochondrial membrane potential), and cell death (apoptosis, pyroptosis, and necrosis). CD-NPs-induced fibrosis model cells had stronger proliferation, migration, and invasion than did CD-MPs. In in vivo experiments, lung coefficient, alveolar inflammation score, and lung tissue fibrosis score (mean: 1.1%, 1.33, 1.33) of CD-NPs were higher than those of CD-MPs (mean: 1.3%, 2.67, 2.67). CD-NPs accelerated the progression of pulmonary fibrosis by upregulating the expression of pro-fibrotic proteins and promoting epithelial-mesenchymal transition. The regulatory molecules involved were E-cadherin, N-cadherin, COL-1, COL-3, ZO-1, ZEB1, Slug, α-SMA, TGFβ1, and Vimentin.ConclusionsStimulation with CD-NPs resulted in more pronounced acute and chronic lung toxicity than did stimulation with CD-MPs. These effects included acute inflammatory response, mitochondrial damage, pyroptosis, and necrosis, and more pulmonary fibrosis induced by epithelial-mesenchymal transition.

Dataset Information

Decreased reticuloendothelial system clearance and increased blood half-life and immune cell labeling for nano- and micron-sized superparamagnetic iron-oxide particles upon pre-treatment with Intralipid.

Publications

Decreased reticuloendothelial system clearance and increased blood half-life and immune cell labeling for nano- and micron-sized superparamagnetic iron-oxide particles upon pre-treatment with Intralipid.

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