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
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, li...
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| Published in | Biochimica et biophysica acta Vol. 1830; no. 6; pp. 3447 - 3453 |
|---|---|
| Main Authors | , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Netherlands
Elsevier B.V
01.06.2013
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| Subjects | |
| Online Access | Get full text |
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| 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.
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► Intralipid targets the liver Kupffer cells and blunts nanoparticle clearance. ► Intralipid results in an ~50% decrease in liver uptake of USPIO and MPIO particles. ► Intralipid produces an ~3-fold increase in blood half-life of the particles. ► Intralipid causes a 2 to 5-fold increase in labeling efficiency of blood monocytes. ► Nanoparticles can target more diverse sites or organs, other than the liver. |
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| AbstractList | 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.
[Display omitted]
► Intralipid targets the liver Kupffer cells and blunts nanoparticle clearance. ► Intralipid results in an ~50% decrease in liver uptake of USPIO and MPIO particles. ► Intralipid produces an ~3-fold increase in blood half-life of the particles. ► Intralipid causes a 2 to 5-fold increase in labeling efficiency of blood monocytes. ► Nanoparticles can target more diverse sites or organs, other than the liver. 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. BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. GENERAL SIGNIFICANCE: 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. 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.BACKGROUNDSuperparamagnetic 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.METHODSIntralipid 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.RESULTSPre-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.CONCLUSIONSIntralipid 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.GENERAL SIGNIFICANCEOur 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. 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. |
| Author | Liu, Li Foley, Lesley M. Yeh, Fang-Cheng Prior, Devin E. Li, Wendy F. Barbe, Brent Bain, Daniel J. Hitchens, T. Kevin Ye, Qing Ho, Chien Wu, Yijen |
| AuthorAffiliation | b Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA a Pittsburgh NMR Center for Biomedical Research and Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA c Department of Geology and Planetary Science, University of Pittsburgh, Pittsburgh, PA |
| AuthorAffiliation_xml | – name: c Department of Geology and Planetary Science, University of Pittsburgh, Pittsburgh, PA – name: b Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA – name: a Pittsburgh NMR Center for Biomedical Research and Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA |
| Author_xml | – sequence: 1 givenname: Li surname: Liu fullname: Liu, Li organization: Pittsburgh NMR Center for Biomedical Research and Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA – sequence: 2 givenname: T. Kevin surname: Hitchens fullname: Hitchens, T. Kevin organization: Pittsburgh NMR Center for Biomedical Research and Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA – sequence: 3 givenname: Qing surname: Ye fullname: Ye, Qing organization: Pittsburgh NMR Center for Biomedical Research and Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA – sequence: 4 givenname: Yijen surname: Wu fullname: Wu, Yijen organization: Pittsburgh NMR Center for Biomedical Research and Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA – sequence: 5 givenname: Brent surname: Barbe fullname: Barbe, Brent organization: Pittsburgh NMR Center for Biomedical Research and Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA – sequence: 6 givenname: Devin E. surname: Prior fullname: Prior, Devin E. organization: Pittsburgh NMR Center for Biomedical Research and Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA – sequence: 7 givenname: Wendy F. surname: Li fullname: Li, Wendy F. organization: Pittsburgh NMR Center for Biomedical Research and Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA – sequence: 8 givenname: Fang-Cheng surname: Yeh fullname: Yeh, Fang-Cheng organization: Pittsburgh NMR Center for Biomedical Research and Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA – sequence: 9 givenname: Lesley M. surname: Foley fullname: Foley, Lesley M. organization: Pittsburgh NMR Center for Biomedical Research and Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA – sequence: 10 givenname: Daniel J. surname: Bain fullname: Bain, Daniel J. organization: Department of Geology and Planetary Science, University of Pittsburgh, Pittsburgh, PA, USA – sequence: 11 givenname: Chien surname: Ho fullname: Ho, Chien email: chienho@andrew.cmu.edu organization: Pittsburgh NMR Center for Biomedical Research and Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/23396002$$D View this record in MEDLINE/PubMed |
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| Keywords | PBS r2 RES Intralipid FDA MRI Blood half-life BN ppm USPIO MPIO RES clearance Nanoparticles FITC PEG ICP-MS Labeling of immune cells |
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| Notes | http://dx.doi.org/10.1016/j.bbagen.2013.01.021 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Devin Elizabeth Prior’s current address: College of Medicine, Ohio State University, Columbus, OH |
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| SubjectTerms | Animals bioavailability Biological Availability biosensors blood circulation Blood half-life Contrast Media - pharmacokinetics Contrast Media - pharmacology drug delivery systems drugs Emulsions - pharmacokinetics Emulsions - pharmacology Fat Emulsions, Intravenous - pharmacokinetics Fat Emulsions, Intravenous - pharmacology Ferric Compounds - pharmacokinetics Ferric Compounds - pharmacology flow cytometry Half-Life hepatocytes histology image analysis Intralipid intravenous injection iron iron oxides Kupffer cells Kupffer Cells - cytology Kupffer Cells - metabolism Labeling of immune cells liver Liver - cytology Liver - metabolism magnetic resonance imaging Magnetite Nanoparticles Male monocytes Nanoparticles Phospholipids - pharmacokinetics Phospholipids - pharmacology pretreatment Rats Rats, Inbred BN RES clearance Soybean Oil - pharmacokinetics Soybean Oil - pharmacology |
| Title | 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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