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

  title={Slow intracellular trafficking of catalase nanoparticles targeted to ICAM-1 protects endothelial cells from oxidative stress.},
  author={Silvia Muro and Xiumin Cui and C. VanelleandD. Gajewski and J C Murciano and Vladimir R Muzykantov and Michael Koval},
  journal={American journal of physiology. Cell physiology},
  volume={285 5},
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… 

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

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.

Control of intracellular trafficking of ICAM-1-targeted nanocarriers by endothelial Na+/H+ exchanger proteins.

NHE1 and NHE6 regulate distinct phases ofAnti-ICAM/NC uptake and trafficking; pharmacological agents affecting these regulatory elements alter the itinerary of anti-ICam/NC intracellular trafficking; and these agents modulate duration of the therapeutic effects of targeted drugs.

ICAM-1 targeting, intracellular trafficking, and functional activity of polymer nanocarriers coated with a fibrinogen-derived peptide for lysosomal enzyme replacement

Polymer nanocarriers coated with antibody against intercellular adhesion molecule 1 (ICAM-1), a protein overexpressed on most cells under disease states, enhanced biodistribution and lysosomal delivery of these therapeutics.

Distinct Subcellular Trafficking Resulting from Monomeric vs Multimeric Targeting to Endothelial ICAM-1: Implications for Drug Delivery

In conclusion, ICAM-1 can mediate different intracellular itineraries, revealing new insight into this biological pathway and alternative avenues for drug delivery.

Control of endothelial targeting and intracellular delivery of therapeutic enzymes by modulating the size and shape of ICAM-1-targeted carriers.

Carrier geometry was found to influence endothelial targeting in the vasculature, and the rate of endocytosis and lysosomal transport within ECs, and rational design of carrier geometry will help optimize endothelium-targeted therapeutics.

Lysosomal enzyme delivery by ICAM-1-targeted nanocarriers bypassing glycosylation- and clathrin-dependent endocytosis.


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Flow shear stress differentially regulates endothelial uptake of nanocarriers targeted to distinct epitopes of PECAM-1.

Differential intra-endothelial delivery of polymer nanocarriers targeted to distinct PECAM-1 epitopes.




A novel endocytic pathway induced by clustering endothelial ICAM-1 or PECAM-1

Interestingly, these kinases are part of the signal transduction pathways that are activated when circulating leukocytes engage endothelial cell adhesion molecules, suggesting the possibility that CAM-mediated endocytosis is regulated using comparable signaling pathways.

ICAM-directed vascular immunotargeting of antithrombotic agents to the endothelial luminal surface.

Drug targeting to a highly expressed, noninternalizable determinant up-regulated on the perturbed endothelium may help to manage inflammation and thrombosis and enhanced drug delivery to sites of inflammation and the potential anti-inflammatory effect of blocking ICAM-1 may enhance the benefit of this targeting strategy.

Cell‐selective intracellular delivery of a foreign enzyme to endothelium in vivo using vascular immunotargeting

PECAM‐directed vascular immunotargeting of a reporter enzyme (β‐galactosidase, β‐Gal), a feasible strategy for cell‐selective, intracellular delivery of an active foreign enzyme to endothelial cells in vivo, may be potentially useful for the treatment of acute pulmonary or vascular diseases.

Immunotargeting of glucose oxidase to endothelium in vivo causes oxidative vascular injury in the lungs.

Anti-PECAM-GOX provides a novel model of oxidative injury to the pulmonary endothelium in vivo and indicates that an immunotargeting strategy can deliver an active enzyme to selected target cells in intact animals.

Immunotargeting of catalase to ACE or ICAM-1 protects perfused rat lungs against oxidative stress.

The results support a strategy of catalase immunotargeting for protection against pulmonary oxidative injury and confirm the specificity of the effect of MAb-catalase.

Rapid endo‐lysosomal escape of poly(DL‐lactide‐coglycolide) nanoparticles: implications for drug and gene delivery

The mechanism of rapid escape is by selective reversal of the surface charge of NPs (from anionic to cationic) in the acidic endolysosomal compartment, which causes the NPs to interact with the endo‐lysosomal membrane and escape into the cytosol.

Size of IgG-opsonized particles determines macrophage response during internalization.

With increasing particle size, IgG-opsonized particle uptake became less clathrin dependent and more actin dependent, which suggests that phagocytic cups may be important in the rapid delivery of internalized particles to lysosomes.

Immunotargeting of catalase to the pulmonary endothelium alleviates oxidative stress and reduces acute lung transplantation injury

Findings validate the therapeutic potential of vascular immunotargeting as a drug delivery strategy to reduce endothelial injury and potential applications of this strategy include improving the outcome of clinical lung transplantation and treating a wide variety of endothelial disorders.

Targeting of superoxide dismutase and catalase to vascular endothelium.

  • V. Muzykantov
  • Biology
    Journal of controlled release : official journal of the Controlled Release Society
  • 2001

Oligomerized transferrin receptors are selectively retained by a lumenal sorting signal in a long-lived endocytic recycling compartment

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