title: Immunoliposomal drug-delivery system targeting lectin-like oxidized low-density lipoprotein receptor-1 for carotid plaque lesions in rats.
abstract: OBJECTIVE
  Targeted drug delivery with immunoliposomes has been applied to various in vivo animal models and is newly focused as a novel therapeutic target. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX1) is a potent regulator of systemic atherosclerosis, and the authors focused on its effect on carotid plaques. The authors developed a LOX1-targeted liposomal rho-kinase inhibitor and examined the therapeutic effect on carotid intimal hypertrophy in rats.
  
  
  METHODS
  LOX1-targeted rho-kinase inhibitor fasudil-containing liposomes, composed of hydrogenated soy phosphatidylcholine/cholesterol/PEG(2000)-DSPE, were prepared by conjugating anti-LOX1 antibodies on the surface and by remote loading of fasudil. Carotid intimal hypertrophy was induced by balloon injury, and the drugs were intravenously administered on Day 3 postinjury. The rats were divided into 4 groups: nontreatment, treatment with intravenous fasudil (2 mg), treatment with liposomal fasudil (2 mg), and treatment with LOX1-targeted liposomal fasudil (2 mg). The authors compared intimal hypertrophy, atherosclerotic factor, and matrix metalloproteinase-9 expression among groups.
  
  
  RESULTS
  DiI-labeled LOX1-targeted liposomes were prominently observed in the lesions on Day 7 after the surgery. The intimal thickness was significantly reduced in the LOX1-targeted liposomal fasudil-treated group (mean 81.6 ± 13.9 μm) compared with the other groups (no treatment 105.4 ± 16.8 μm; fasudil treatment 102.4 ± 20.0 μm; and liposomal fasudil treatment 102.8 ± 22.2 μm; p = 0.046). Matrix metalloproteinase-9 expression was also significantly reduced in the LOX1-targeted liposomal fasudil group.
  
  
  CONCLUSIONS
  Liposomes conjugated with anti-LOX1 antibody effectively reached carotid artery lesions, and liposomal rho-kinase significantly inhibited intimal hypertrophy. The new liposomal drug delivery system targeting LOX1 may become a therapeutic strategy for atherosclerotic diseases.
authors.affiliation: Tohoku University Hospital, Emergency Center, Tohoku University Graduate School of Medicine, Sendai, Japan. satsushi2002@yahoo.co.jp
authors.forename: Atsushi
authors.initials: A
authors.lastname: Saito
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimizu
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Doi
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Ishida
authors.forename: Miki
authors.initials: M
authors.lastname: Fujimura
authors.forename: Takashi
authors.initials: T
authors.lastname: Inoue
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiwada
authors.forename: Teiji
authors.initials: T
authors.lastname: Tominaga
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D002340:Carotid Artery Diseases / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D017536:Carotid Artery, Common / Q000276:immunology* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D008081:Liposomes / Q000276:immunology*; D008297:Male; D058226:Plaque, Atherosclerotic / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051127:Scavenger Receptors, Class E / Q000378:metabolism*
chemical_list: D008081:Liposomes; D051127:Scavenger Receptors, Class E; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C049347:fasudil