Linked Life Data

16505161

Source:http://linkedlifedata.com/resource/pubmed/id/16505161

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-5-19
pubmed:abstractText
Targeting of diagnostic and therapeutic agents to endothelial cells (ECs) provides an avenue to improve treatment of many maladies. For example, intercellular adhesion molecule 1 (ICAM-1), a constitutive endothelial cell adhesion molecule up-regulated in many diseases, is a good determinant for endothelial targeting of therapeutic enzymes and polymer nanocarriers (PNCs) conjugated with anti-ICAM (anti-ICAM/PNCs). However, intrinsic and extrinsic factors that control targeting of anti-ICAM/PNCs to ECs (e.g., anti-ICAM affinity and PNC valency and flow) have not been defined. In this study we tested in vitro and in vivo parameters of targeting to ECs of anti-ICAM/PNCs consisting of either prototype polystyrene or biodegradable poly(lactic-coglycolic) acid polymers (approximately 200 nm diameter spheres carrying approximately 200 anti-ICAM molecules). Anti-ICAM/PNCs, but not control IgG/PNCs 1) rapidly (t1/2 approximately 5 min) and specifically bound to tumor necrosis factor-activated ECs in a dose-dependent manner (Bmax approximately 350 PNC/cell) at both static and physiological shear stress conditions and 2) bound to ECs and accumulated in the pulmonary vasculature after i.v. injection in mice. Anti-ICAM/PNCs displayed markedly higher EC affinity versus naked anti-ICAM (Kd approximately 80 pM versus approximately 8 nM) in cell culture and, probably because of this factor, higher value (185.3 +/- 24.2 versus 50.5 +/- 1.5% injected dose/g) and selectivity (lung/blood ratio 81.0 +/- 10.9 versus 2.1 +/- 0.02, in part due to faster blood clearance) of pulmonary targeting. These results 1) show that reformatting monomolecular anti-ICAM into high-affinity multivalent PNCs boosts their vascular immuno-targeting, which withstands physiological hydrodynamics and 2) support potential anti-ICAM/PNCs utility for medical applications.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
317
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1161-9
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:16505161-Animals, pubmed-meshheading:16505161-Antibodies, Monoclonal, pubmed-meshheading:16505161-Antibody Affinity, pubmed-meshheading:16505161-Drug Carriers, pubmed-meshheading:16505161-Endothelial Cells, pubmed-meshheading:16505161-Endothelium, Vascular, pubmed-meshheading:16505161-Glycolates, pubmed-meshheading:16505161-Humans, pubmed-meshheading:16505161-Intercellular Adhesion Molecule-1, pubmed-meshheading:16505161-Lactic Acid, pubmed-meshheading:16505161-Male, pubmed-meshheading:16505161-Mice, pubmed-meshheading:16505161-Mice, Inbred C57BL, pubmed-meshheading:16505161-Nanostructures, pubmed-meshheading:16505161-Particle Size, pubmed-meshheading:16505161-Polyglycolic Acid, pubmed-meshheading:16505161-Polymers, pubmed-meshheading:16505161-Polystyrenes, pubmed-meshheading:16505161-Rats, pubmed-meshheading:16505161-Rats, Sprague-Dawley
pubmed:year
2006
pubmed:articleTitle
Endothelial targeting of high-affinity multivalent polymer nanocarriers directed to intercellular adhesion molecule 1.
pubmed:affiliation
Institute for Environmental Medicine, 1 John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA 19104-6068, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural