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Lysosomal Degradation of the Carboxydextran Shell of Coated Superparamagnetic Iron Oxide Nanoparticles and the Fate of Professional Phagocytes

Lunov, O.; Syrovets, T.; Röcker, C.; Tron, K.; Nienhaus, G. U.; Rasche, V.; Mailänder, V.; Landfester, K.; Simmet, T.

Abstract:
Contrast agents based on dextran-coatedsuperparamagneticironoxidenanoparticles (SPIO) are internalized by professionalphagocytes such as hepatic Kupffer cells, yet their role in phagocyte biology remains largely unknown. Here we investigated the effects of the SPIO ferucarbotran on murine Kupffer cells and human macrophages. Intravenous injection of ferucarbotran into mice led to rapid accumulation of the particles in phagocytes and to long-lasting increased iron deposition in liver and kidneys. Macrophages incorporate ferucarbotran in lysosomal vesicles containing alpha-glucosidase, which is capable of degrading the carboxydextranshell of the ferucarbotran particles. Intravenous injection of ferucarbotran into mice followed by incorporation of the nanoparticles into Kupffer cells triggered apoptosis and the subsequent depletion of Kupffer cells. In macrophages, the proinflammatory cytokine TNF-alpha increased the apoptosis rate, the reactive oxygen species production and the activation of c-Jun N-terminal kinase elicited by ferucarbotran, which might be mediated by the induction of cytoplasmic phospholipase A2 by TNF-alpha. Notably ... mehr



Originalveröffentlichung
DOI: 10.1016/j.biomaterials.2010.08.003
Scopus
Zitationen: 109
Web of Science
Zitationen: 106
Zugehörige Institution(en) am KIT Institut für Angewandte Physik (APH)
Publikationstyp Zeitschriftenaufsatz
Jahr 2010
Sprache Englisch
Identifikator ISSN: 0142-9612
KITopen-ID: 1000027204
Erschienen in Biomaterials
Band 31
Heft 34
Seiten 9015 - 9022
Nachgewiesen in Web of Science
Scopus
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