Slow intracellular trafficking of catalase nanoparticles targeted to ICAM-1 protects endothelial cells from oxidative stress.

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TitleSlow intracellular trafficking of catalase nanoparticles targeted to ICAM-1 protects endothelial cells from oxidative stress.
Publication TypeJournal Article
Year of Publication2003
AuthorsMuro, S, Cui, X, Gajewski, C, Murciano, J-C, Muzykantov, VR, Koval, M
JournalAm J Physiol Cell Physiol
Volume285
Issue5
PaginationC1339-47
Date Published2003 Nov
ISSN0363-6143
KeywordsCatalase, Cells, Cultured, Drug Delivery Systems, Endothelium, Vascular, Humans, Intercellular Adhesion Molecule-1, Intracellular Fluid, Nanotechnology, Oxidative Stress, Protein Transport
Abstract

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.

DOI10.1152/ajpcell.00099.2003
Alternate JournalAm. J. Physiol., Cell Physiol.
PubMed ID12878488
Grant ListGM 61012 / GM / NIGMS NIH HHS / United States
HL 60290 / HL / NHLBI NIH HHS / United States
P01 HL 19737-26 / HL / NHLBI NIH HHS / United States
P01 HL019737-280018 / HL / NHLBI NIH HHS / United States
R01 GM061012-04 / GM / NIGMS NIH HHS / United States