Immunoliposomal drug-delivery system targeting lectin-like oxidized low-density lipoprotein receptor-1 for carotid plaque lesions in rats: Laboratory investigation

Atsushi Saito, Hiroaki Shimizu, Yusuke Doi, Tatsuhiro Ishida, Miki Fujimura, Takashi Inoue, Hiroshi Kiwada, Teiji Tominaga

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

Object. 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/PEG2000-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 mm) 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.

Original languageEnglish
Pages (from-to)720-727
Number of pages8
JournalJournal of neurosurgery
Volume115
Issue number4
DOIs
Publication statusPublished - 2011 Oct

Keywords

  • Atherosclerosis
  • Carotid artery
  • Drug delivery
  • Liposome
  • Matrix metalloproteinase
  • Vascular disorders

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

Fingerprint Dive into the research topics of 'Immunoliposomal drug-delivery system targeting lectin-like oxidized low-density lipoprotein receptor-1 for carotid plaque lesions in rats: Laboratory investigation'. Together they form a unique fingerprint.

Cite this