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The Effect of Carboxydextran-coated Superparamagnetic Iron Oxide Nanoparticles on c-Jun N-terminal Kinase-mediated Apoptosis in Human Macrophages

Lunov, O.; Syrovets, T.; Büchele, B.; Jiang, X.; Röcker, C.; Tron, K.; Nienhaus, G. U.; Walther, P.; Mailänder, V.; Landfester, K.; Simmet, T.

Superparamagneticironoxidenanoparticles are frequently used for cell labeling or as diagnostic contrast media, yet studies analyzing their effects on immune cells remain scarce. Here we investigated how nanosized carboxydextran-coatedsuperparamagneticironoxide (SPIO) and ultrasmall superparamagneticironoxide (USPIO) might affect humanmacrophages. Within 1 h, both SPIO and USPIO were rapidly taken up by macrophages. Confocal microscopy revealed that after 24 h the particles were almost exclusively localized within the lysosomal compartment. Continued cultivation of the macrophages for several days was associated with apoptosis induction caused by a long-lasting activation of the c-JunN-terminalkinase (JNK) pathway. JNK activation was due to significantly elevated levels of reactive oxygen species, whereas no TNF-alpha was produced by the macrophages treated with nanoparticles. Compared to SPIO, USPIO induced more pronounced biochemical alterations and cytotoxicity, which could be antagonized by the JNK inhibitor V. Alternatively, treatment of macrophages with Trolox TM or N-acetyl-l-cysteine, two functionally different scavengers of ... mehr

DOI: 10.1016/j.biomaterials.2010.03.023
Zitationen: 102
Web of Science
Zitationen: 97
Zugehörige Institution(en) am KIT Institut für Angewandte Physik (APH)
Publikationstyp Zeitschriftenaufsatz
Jahr 2010
Sprache Englisch
Identifikator ISSN: 0142-9612
KITopen-ID: 1000027191
Erschienen in Biomaterials
Band 31
Heft 19
Seiten 5063 - 5071
Nachgewiesen in Web of Science
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