| Slow intracellular trafficking of catalase nanoparticles targeted to ICAM-1 protects endothelial cells from oxidative stress. | |
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MedLine Citation:
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PMID: 12878488 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Nanotechnologies promise new means for drug delivery. ICAM-1 is a good target for vascular immunotargeting of nanoparticles to the perturbed endothelium, although endothelial cells do not internalize monomeric anti-ICAM-1 antibodies. However, coupling ICAM-1 antibodies to nanoparticles creates multivalent ligands that enter cells via an amiloride-sensitive endocytic pathway that does not require clathrin or caveolin. Fluorescence microscopy revealed that internalized anti-ICAM nanoparticles are retained in a stable form in early endosomes for an unusually long time (1-2 h) and subsequently were degraded following slow transport to lysosomes. Inhibition of lysosome acidification by chloroquine delayed degradation without affecting anti-ICAM trafficking. Also, the microtubule disrupting agent nocodazole delayed degradation by inhibiting anti-ICAM nanoparticle trafficking to lysosomes. Addition of catalase to create anti-ICAM nanoparticles with antioxidant activity did not affect the mechanisms of nanoparticle uptake or trafficking. Intracellular anti-ICAM/catalase nanoparticles were active, because endothelial cells were resistant to H2O2-induced oxidative injury for 1-2 h after nanoparticle uptake. Chloroquine and nocodazole increased the duration of antioxidant protection by decreasing the extent of anti-ICAM/catalase degradation. Therefore, the unique trafficking pathway followed by internalized anti-ICAM nanoparticles seems well suited for targeted delivery of therapeutic enzymes to endothelial cells and may provide a basis for treatment of acute vascular oxidative stress. |
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Authors:
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Silvia Muro; Xiumin Cui; Christine Gajewski; Juan-Carlos Murciano; Vladimir R Muzykantov; Michael Koval |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. Date: 2003-07-23 |
Journal Detail:
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Title: American journal of physiology. Cell physiology Volume: 285 ISSN: 0363-6143 ISO Abbreviation: Am. J. Physiol., Cell Physiol. Publication Date: 2003 Nov |
Date Detail:
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Created Date: 2003-10-08 Completed Date: 2003-12-02 Revised Date: 2010-08-09 |
Medline Journal Info:
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Nlm Unique ID: 100901225 Medline TA: Am J Physiol Cell Physiol Country: United States |
Other Details:
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Languages: eng Pagination: C1339-47 Citation Subset: IM |
Affiliation:
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Institute for Environmental Medicine, University of Pennsylvania School of Medicine, 1 John Morgan/6068, 3620 Hamilton Walk, Philadelphia, PA 19104, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Catalase
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administration & dosage* Cells, Cultured Drug Delivery Systems / methods* Endothelium, Vascular / drug effects*, enzymology Humans Intercellular Adhesion Molecule-1 / metabolism* Intracellular Fluid / drug effects Nanotechnology / methods Oxidative Stress / drug effects*, physiology Protein Transport / drug effects, physiology |
| Grant Support | |
ID/Acronym/Agency:
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GM 61012/GM/NIGMS NIH HHS; HL 60290/HL/NHLBI NIH HHS; P01 HL 19737-26/HL/NHLBI NIH HHS; P01 HL019737-280018/HL/NHLBI NIH HHS; R01 GM061012-04/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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126547-89-5/Intercellular Adhesion Molecule-1; EC 1.11.1.6/Catalase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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