TY - JOUR
T1 - Intramural delivery of rapamycin with αvβ3-targeted paramagnetic nanoparticles inhibits stenosis after balloon injury
AU - Cyrus, Tillmann
AU - Zhang, Huiying
AU - Allen, John S.
AU - Williams, Todd A.
AU - Hu, Grace
AU - Caruthers, Shelton D.
AU - Wickline, Samuel A.
AU - Lanza, Gregory M.
PY - 2008/5
Y1 - 2008/5
N2 - BACKGROUND - Drug eluting stents prevent vascular restenosis but can delay endothelial healing. A rabbit femoral artery model of stenosis formation after vascular injury was used to study the effect of intramural delivery of αvβ3-integrin-targeted rapamycin nanoparticles on vascular stenosis and endothelial healing responses. METHODS AND RESULTS - Femoral arteries of 48 atherosclerotic rabbits underwent balloon stretch injury and were locally treated with either (1) αvβ3-targeted rapamycin nanoparticles, (2) αvβ3-targeted nanoparticles without rapamycin, (3) nontargeted rapamycin nanoparticles, or (4) saline. Intramural binding of integrin-targeted paramagnetic nanoparticles was confirmed with MR molecular imaging (1.5 T). MR angiograms were indistinguishable between targeted and control arteries at baseline, but 2 weeks later they showed qualitatively less luminal plaque in the targeted rapamycin treated segments compared with contralateral control vessels. In a first cohort of 19 animals (38 vessel segments), microscopic morphometric analysis of the rapamycin-treated segments revealed a 52% decrease in the neointima/media ratio (P<0.05) compared to control. No differences (P>0.05) were observed among balloon injured vessel segments treated with αvβ3-targeted nanoparticles without rapamycin, nontargeted nanoparticles with rapamycin, or saline. In a second cohort of 29 animals, endothelial healing followed a parallel pattern over 4 weeks in the vessels treated with αvβ3-targeted rapamycin nanoparticles and the 3 control groups. CONCLUSIONS - Local intramural delivery of αvβ3-targeted rapamycin nanoparticles inhibited stenosis without delaying endothelial healing after balloon injury.
AB - BACKGROUND - Drug eluting stents prevent vascular restenosis but can delay endothelial healing. A rabbit femoral artery model of stenosis formation after vascular injury was used to study the effect of intramural delivery of αvβ3-integrin-targeted rapamycin nanoparticles on vascular stenosis and endothelial healing responses. METHODS AND RESULTS - Femoral arteries of 48 atherosclerotic rabbits underwent balloon stretch injury and were locally treated with either (1) αvβ3-targeted rapamycin nanoparticles, (2) αvβ3-targeted nanoparticles without rapamycin, (3) nontargeted rapamycin nanoparticles, or (4) saline. Intramural binding of integrin-targeted paramagnetic nanoparticles was confirmed with MR molecular imaging (1.5 T). MR angiograms were indistinguishable between targeted and control arteries at baseline, but 2 weeks later they showed qualitatively less luminal plaque in the targeted rapamycin treated segments compared with contralateral control vessels. In a first cohort of 19 animals (38 vessel segments), microscopic morphometric analysis of the rapamycin-treated segments revealed a 52% decrease in the neointima/media ratio (P<0.05) compared to control. No differences (P>0.05) were observed among balloon injured vessel segments treated with αvβ3-targeted nanoparticles without rapamycin, nontargeted nanoparticles with rapamycin, or saline. In a second cohort of 29 animals, endothelial healing followed a parallel pattern over 4 weeks in the vessels treated with αvβ3-targeted rapamycin nanoparticles and the 3 control groups. CONCLUSIONS - Local intramural delivery of αvβ3-targeted rapamycin nanoparticles inhibited stenosis without delaying endothelial healing after balloon injury.
KW - Drug delivery
KW - MRI
KW - Nanoparticles
KW - Rapamycin
KW - Restenosis
UR - http://www.scopus.com/inward/record.url?scp=42149149916&partnerID=8YFLogxK
U2 - 10.1161/ATVBAHA.107.156281
DO - 10.1161/ATVBAHA.107.156281
M3 - Article
C2 - 18292395
AN - SCOPUS:42149149916
SN - 1079-5642
VL - 28
SP - 820
EP - 826
JO - Arteriosclerosis, thrombosis, and vascular biology
JF - Arteriosclerosis, thrombosis, and vascular biology
IS - 5
ER -