ICAM-1 recycling in endothelial cells: a novel pathway for sustained intracellular delivery and prolonged effects of drugs.

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TitleICAM-1 recycling in endothelial cells: a novel pathway for sustained intracellular delivery and prolonged effects of drugs.
Publication TypeJournal Article
Year of Publication2005
AuthorsMuro, S, Gajewski, C, Koval, M, Muzykantov, VR
JournalBlood
Volume105
Issue2
Pagination650-8
Date Published2005 Jan 15
ISSN0006-4971
KeywordsAnimals, Catalase, Cell Membrane, Cells, Cultured, Drug Delivery Systems, Endocytosis, Endothelium, Vascular, Humans, Intercellular Adhesion Molecule-1, Iodine Radioisotopes, Lysosomes, Mice, Mice, Inbred C57BL, Microspheres, Oxidative Stress, Protein Transport, Umbilical Veins
Abstract

Intercellular adhesion molecule-1 (ICAM-1) is a target for drug delivery to endothelial cells (ECs), which internalize multivalent anti-ICAM nanocarriers (anti-ICAM/NCs) within 15 to 30 minutes. The concomitant ICAM-1 disappearance from the EC surface transiently inhibited subsequent binding and uptake of anti-ICAM/NCs. Within 1 hour, internalized ICAM-1 diverged from anti-ICAM/NCs into prelysosomal vesicles, resurfaced, and enabled uptake of a subsequent anti-ICAM/NC dose. Thus, internalized ICAM-1 was able to recycle back to the plasma membrane. In vivo pulmonary targeting of a second anti-ICAM/NC dose injected 15 minutes after the first dose was decreased by 50% but recovered between 30 minutes and 2.5 hours, comparable to cultured ECs. Anti-ICAM/NCs affected neither EC viability nor fluid-phase endocytosis and traffic to lysosomes. However, lysosomal trafficking of the second dose of anti-ICAM/NCs was decelerated at least 2-fold versus the first dose; hence the major fraction of anti-ICAM/NCs resided in prelysosomal vesicles for at least 5 hours without degradation. Two successive doses of anti-ICAM/NC/catalase protected ECs against H2O2 for at least 8 hours versus 2 hours afforded by a single dose, suggesting that recurrent targeting to ICAM-1 affords longer effects. ICAM-1 recycling and inhibited lysosomal traffic/degradation of subsequent doses may help to prolong activity of therapeutic agents delivered into ECs by anti-ICAM/NCs.

DOI10.1182/blood-2004-05-1714
Alternate JournalBlood
PubMed ID15367437
Grant ListGM61012 / GM / NIGMS NIH HHS / United States
HL/GM 71175-01 / HL / NHLBI NIH HHS / United States
P01 HL019737-26 / HL / NHLBI NIH HHS / United States
P01 HL019737-290018 / HL / NHLBI NIH HHS / United States
R01 GM061012-06 / GM / NIGMS NIH HHS / United States