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

J Neurosurg. 2011 Oct;115(4):720-7. doi: 10.3171/2011.5.JNS10227. Epub 2011 Jun 17.


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/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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / administration & dosage
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives*
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / therapeutic use
  • Animals
  • Carotid Artery Diseases / immunology
  • Carotid Artery Diseases / metabolism
  • Carotid Artery Diseases / therapy*
  • Carotid Artery, Common / immunology*
  • Carotid Artery, Common / metabolism
  • Drug Delivery Systems / methods*
  • Liposomes / immunology*
  • Male
  • Plaque, Atherosclerotic / immunology
  • Plaque, Atherosclerotic / metabolism
  • Plaque, Atherosclerotic / therapy*
  • Rats
  • Rats, Sprague-Dawley
  • Scavenger Receptors, Class E / metabolism*


  • Liposomes
  • Scavenger Receptors, Class E
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • fasudil