title: Multi-ligand poly(L-lactic-co-glycolic acid) nanoparticles inhibit activation of endothelial cells.
abstract: Endothelial cell (EC) activation and inflammation is a key step in the initiation and progression of many cardiovascular diseases. Targeted delivery of therapeutic reagents to inflamed EC using nanoparticles is challenging as nanoparticles do not arrest on EC efficiently under high shear stress. In this study, we developed a novel polymeric platelet-mimicking nanoparticle for strong particle adhesion onto ECs and enhanced particle internalization by ECs. This nanoparticle was encapsulated with dexamethasone as the anti-inflammatory drug, and conjugated with polyethylene glycol, glycoprotein 1b, and trans-activating transcriptional peptide. The multi-ligand nanoparticle showed significantly greater adhesion on P-selectin, von Willebrand Factor, than the unmodified particles, and activated EC in vitro under both static and flow conditions. Treatment of injured rat carotid arteries with these multi-ligand nanoparticles suppressed neointimal stenosis more than unconjugated nanoparticles did. These results indicate that this novel multi-ligand nanoparticle is efficient to target inflamed EC and inhibit inflammation and subsequent stenosis.
authors: Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors: Hao
authors: H
authors: Xu
authors: Soujanya
authors: S
authors: Kona
authors: Lee-Chun
authors: LC
authors: Su
authors: Yi-Ting
authors: YT
authors: Tsai
authors: Jing-Fei
authors: JF
authors: Dong
authors: Emmanouil S
authors: ES
authors: Brilakis
authors: Liping
authors: L
authors: Tang
authors: Subhash
authors: S
authors: Banerjee
authors: Kytai T
authors: KT
authors: Nguyen
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D020212:Carotid Artery Injuries / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017536:Carotid Artery, Common / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016893:Carotid Stenosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D002478:Cells, Cultured; D003907:Dexamethasone / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004195:Disease Models, Animal; D004337:Drug Carriers; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D053758:Nanoparticles; D058426:Neointima; D019007:P-Selectin / Q000378:metabolism; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism; D011100:Polyglycolic Acid / Q000737:chemistry / Q000378:metabolism*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D008024:Ligands; D019007:P-Selectin; D019038:Platelet Glycoprotein GPIb-IX Complex; D014841:von Willebrand Factor; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003907:Dexamethasone
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