Journal article
Prevention of vascular inflammation by nanoparticle targeting of adherent neutrophils
Nature nanotechnology, Vol.9(3), pp.204-210
03/2014
Handle:
https://hdl.handle.net/2376/108113
PMCID: PMC4100792
PMID: 24561355
Abstract
Inflammatory diseases such as acute lung injury and ischaemic tissue injury are caused by the adhesion of a type of white blood cell--polymorphonuclear neutrophils--to the lining of the circulatory system or vascular endothelium and unchecked neutrophil transmigration. Nanoparticle-mediated targeting of activated neutrophils on vascular endothelial cells at the site of injury may be a useful means of directly inactivating neutrophil transmigration and hence mitigating vascular inflammation. Here, we report a method employing drug-loaded albumin nanoparticles, which efficiently deliver drugs into neutrophils adherent to the surface of the inflamed endothelium. Using intravital microscopy of tumour necrosis factor-α-challenged mouse cremaster post-capillary venules, we demonstrate that fluorescently tagged albumin nanoparticles are largely internalized by neutrophils adherent to the activated endothelium via cell surface Fcɣ receptors. Administration of albumin nanoparticles loaded with the spleen tyrosine kinase inhibitor, piceatannol, which blocks 'outside-in' β2 integrin signalling in leukocytes, detached the adherent neutrophils and elicited their release into the circulation. Thus, internalization of drug-loaded albumin nanoparticles into neutrophils inactivates the pro-inflammatory function of activated neutrophils, thereby offering a promising approach for treating inflammatory diseases resulting from inappropriate neutrophil sequestration and activation.
Metrics
12 Record Views
Details
- Title
- Prevention of vascular inflammation by nanoparticle targeting of adherent neutrophils
- Creators
- Zhenjia Wang - 1] Department of Pharmacology, University of Illinois Chicago College of Medicine, Chicago, Illinois 60612, USA Center for Lung and Vascular Biology, University of Illinois Chicago College of Medicine, Chicago, Illinois 60612, USAJing Li - Department of Pharmacology, University of Illinois Chicago College of Medicine, Chicago, Illinois 60612, USAJaehyung Cho - 1] Department of Pharmacology, University of Illinois Chicago College of Medicine, Chicago, Illinois 60612, USA Center for Lung and Vascular Biology, University of Illinois Chicago College of Medicine, Chicago, Illinois 60612, USA Department of Anesthesiology, University of Illinois Chicago College of Medicine, Chicago, Illinois 60612, USAAsrar B Malik - 1] Department of Pharmacology, University of Illinois Chicago College of Medicine, Chicago, Illinois 60612, USA Center for Lung and Vascular Biology, University of Illinois Chicago College of Medicine, Chicago, Illinois 60612, USA
- Publication Details
- Nature nanotechnology, Vol.9(3), pp.204-210
- Academic Unit
- Pharmaceutical Sciences, Department of; Chemical Engineering and Bioengineering, School of
- Publisher
- England
- Grant note
- K25 HL111157 / NHLBI NIH HHS R01 HL090152 / NHLBI NIH HHS P01 HL077806 / NHLBI NIH HHS R01 HL109439 / NHLBI NIH HHS P01HL77806 / NHLBI NIH HHS K25HL111157 / NHLBI NIH HHS
- Identifiers
- 99900547498101842
- Language
- English
- Resource Type
- Journal article