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Liver fibrosis affects the targeting properties of drug delivery systems to macrophage subsets in vivo
C. Ergen, PM. Niemietz, F. Heymann, M. Baues, F. Gremse, R. Pola, L. van Bloois, G. Storm, F. Kiessling, C. Trautwein, T. Luedde, T. Lammers, F. Tacke,
Jazyk angličtina Země Nizozemsko
Typ dokumentu časopisecké články, práce podpořená grantem
- MeSH
- fluorescenční mikroskopie MeSH
- imunohistochemie MeSH
- jaterní cirhóza metabolismus MeSH
- lékové transportní systémy MeSH
- liposomy chemie MeSH
- lymfocyty metabolismus MeSH
- makrofágy metabolismus MeSH
- mikrobubliny MeSH
- myši MeSH
- nanomedicína MeSH
- polymery chemie MeSH
- průtoková cytometrie MeSH
- rentgenová mikrotomografie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Myeloid immune cells promote inflammation and fibrosis in chronic liver diseases. Drug delivery systems, such as polymers, liposomes and microbubbles, efficiently target myeloid cells in healthy liver, but their targeting properties in hepatic fibrosis remain elusive. We therefore studied the biodistribution of three intravenously injected carrier material, i.e. 10 nm poly(N-(2-hydroxypropyl)methacrylamide) polymers, 100 nm PEGylated liposomes and 2000 nm poly(butyl cyanoacrylate) microbubbles, in two fibrosis models in immunocompetent mice. While whole-body imaging confirmed preferential hepatic uptake even after induction of liver fibrosis, flow cytometry and immunofluorescence analysis revealed markedly decreased carrier uptake by liver macrophage subsets in fibrosis, particularly for microbubbles and polymers. Importantly, carrier uptake co-localized with immune infiltrates in fibrotic livers, corroborating the intrinsic ability of the carriers to target myeloid cells in areas of inflammation. Of the tested carrier systems liposomes had the highest uptake efficiency among hepatic myeloid cells, but the lowest specificity for cellular subsets. Hepatic fibrosis affected carrier uptake in liver and partially in spleen, but not in other tissues (blood, bone marrow, lung, kidney). In conclusion, while drug carrier systems target distinct myeloid cell populations in diseased and healthy livers, hepatic fibrosis profoundly affects their targeting efficiency, supporting the need to adapt nanomedicine-based approaches in chronic liver disease.
Department of Hepatology and Gastroenterology Charité University Medicine Berlin Berlin Germany
Department of Medicine 1 University Hospital Hamburg Eppendorf Hamburg Germany
Department of Medicine 3 University Hospital Aachen Aachen Germany
Citace poskytuje Crossref.org
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- $a Ergen, Can $u Department of Medicine I, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Department of Medicine III, University Hospital Aachen, Aachen, Germany.
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- $a Liver fibrosis affects the targeting properties of drug delivery systems to macrophage subsets in vivo / $c C. Ergen, PM. Niemietz, F. Heymann, M. Baues, F. Gremse, R. Pola, L. van Bloois, G. Storm, F. Kiessling, C. Trautwein, T. Luedde, T. Lammers, F. Tacke,
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- $a Myeloid immune cells promote inflammation and fibrosis in chronic liver diseases. Drug delivery systems, such as polymers, liposomes and microbubbles, efficiently target myeloid cells in healthy liver, but their targeting properties in hepatic fibrosis remain elusive. We therefore studied the biodistribution of three intravenously injected carrier material, i.e. 10 nm poly(N-(2-hydroxypropyl)methacrylamide) polymers, 100 nm PEGylated liposomes and 2000 nm poly(butyl cyanoacrylate) microbubbles, in two fibrosis models in immunocompetent mice. While whole-body imaging confirmed preferential hepatic uptake even after induction of liver fibrosis, flow cytometry and immunofluorescence analysis revealed markedly decreased carrier uptake by liver macrophage subsets in fibrosis, particularly for microbubbles and polymers. Importantly, carrier uptake co-localized with immune infiltrates in fibrotic livers, corroborating the intrinsic ability of the carriers to target myeloid cells in areas of inflammation. Of the tested carrier systems liposomes had the highest uptake efficiency among hepatic myeloid cells, but the lowest specificity for cellular subsets. Hepatic fibrosis affected carrier uptake in liver and partially in spleen, but not in other tissues (blood, bone marrow, lung, kidney). In conclusion, while drug carrier systems target distinct myeloid cell populations in diseased and healthy livers, hepatic fibrosis profoundly affects their targeting efficiency, supporting the need to adapt nanomedicine-based approaches in chronic liver disease.
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- $a Niemietz, Patricia Maria $u Department of Medicine III, University Hospital Aachen, Aachen, Germany.
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- $a Lammers, Twan $u Department of Experimental Molecular Imaging, University Clinic and Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands; Department of Targeted Therapeutics, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, the Netherlands.
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- $a Tacke, Frank $u Department of Medicine III, University Hospital Aachen, Aachen, Germany; Department of Hepatology and Gastroenterology, Charité University Medicine Berlin, Berlin, Germany. Electronic address: frank.tacke@gmx.net.
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