title: Targeting to endothelial cells augments the protective effect of novel dual bioactive antioxidant/anti-inflammatory nanoparticles.
abstract: Oxidative stress and inflammation are intertwined contributors to numerous acute vascular pathologies. A novel dual bioactive nanoparticle with antioxidant/anti-inflammatory properties was developed based on the interactions of tocopherol phosphate and the manganese porphyrin SOD mimetic, MnTMPyP. The size and drug incorporation efficiency were shown to be dependent on the amount of MnTMPyP added as well as the choice of surfactant. MnTMPyP was shown to retain its SOD-like activity while in intact particles and to release in a slow and controlled manner. Conjugation of anti-PECAM antibody to the nanoparticles provided endothelial targeting and potentiated nanoparticle-mediated suppression of inflammatory activation of these cells manifested by expression of VCAM, E-selectin, and IL-8. This nanoparticle technology may find applicability with drug combinations relevant for other pathologies.
authors.affiliation: Department of Pharmacology and Center for Targeted Therapeutics and Translational Nanomedicine, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.
authors.forename: Melissa D
authors.initials: MD
authors.lastname: Howard
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Hood
authors.forename: Colin F
authors.initials: CF
authors.lastname: Greineder
authors.forename: Ivan S
authors.initials: IS
authors.lastname: Alferiev
authors.forename: Michael
authors.initials: M
authors.lastname: Chorny
authors.forename: Vladimir
authors.initials: V
authors.lastname: Muzykantov
mesh_terms: D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000494:pharmacology*; D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology*; D002478:Cells, Cultured; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008665:Metalloporphyrins / Q000737:chemistry / Q000494:pharmacology; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D013482:Superoxide Dismutase / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D019040:E-Selectin; D016209:Interleukin-8; D008665:Metalloporphyrins; C502230:Mn(III) 5,10,15,20-tetrakis(N-methylpyridinium-2-yl)porphyrin; D019010:Vascular Cell Adhesion Molecule-1; D013482:Superoxide Dismutase