TY - JOUR
T1 - Immunoliposomal drug-delivery system targeting lectin-like oxidized low-density lipoprotein receptor-1 for carotid plaque lesions in rats
T2 - Laboratory investigation
AU - Saito, Atsushi
AU - Shimizu, Hiroaki
AU - Doi, Yusuke
AU - Ishida, Tatsuhiro
AU - Fujimura, Miki
AU - Inoue, Takashi
AU - Kiwada, Hiroshi
AU - Tominaga, Teiji
PY - 2011/10
Y1 - 2011/10
N2 - 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.
AB - 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.
KW - Atherosclerosis
KW - Carotid artery
KW - Drug delivery
KW - Liposome
KW - Matrix metalloproteinase
KW - Vascular disorders
UR - http://www.scopus.com/inward/record.url?scp=80053422363&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80053422363&partnerID=8YFLogxK
U2 - 10.3171/2011.5.JNS10227
DO - 10.3171/2011.5.JNS10227
M3 - Article
C2 - 21682565
AN - SCOPUS:80053422363
VL - 115
SP - 720
EP - 727
JO - Journal of Neurosurgery
JF - Journal of Neurosurgery
SN - 0022-3085
IS - 4
ER -