Intramural delivery of rapamycin with αvβ3-targeted paramagnetic nanoparticles inhibits stenosis after balloon injury
Intramural delivery of rapamycin with αvβ3-targeted paramagnetic nanoparticles inhibits stenosis after balloon injury
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DOI：
10.1161/atvbaha.107.156281
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发表时间：
2008-05-01
影响因子：
8.7
通讯作者：
Lanza, Gregory M.
中科院分区：
文献类型：
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作者：
Cyrus, Tillmann;Zhang, Huiying;Lanza, Gregory M.
背景-药物洗脱支架可预防血管再狭窄，但可延缓内皮愈合。方法和结果：48只兔股动脉球囊牵张损伤后，分别用(1)α(V)β(3)靶向雷帕霉素纳米粒、(2)α(V)β(3)靶向雷帕霉素纳米粒、(3)非靶向雷帕霉素纳米粒或(4)生理盐水局部治疗。磁共振分子成像(1.5T)证实了整合素靶向的顺磁性纳米颗粒的壁内结合。磁共振血管成像在基线时不能区分靶动脉和对照动脉，但2周后，与对侧对照血管相比，靶向雷帕霉素治疗的节段显示出定性的较少的管腔斑块。在19只动物(38个血管节段)的第一个队列中，对雷帕霉素处理的节段进行的显微形态计量分析显示，与对照组相比，新生内膜/中膜比率降低了52%(P<；0.05)。在不加雷帕霉素的α(V)β(3)靶向纳米粒、加雷帕霉素的非靶向纳米粒或生理盐水治疗的球囊损伤血管节段之间没有观察到差异(P&gT；0.05)。在由29只动物组成的第二个队列中，接受α(V)β(3)靶向雷帕霉素纳米粒治疗的血管和3个对照组的血管内皮细胞愈合在4周内遵循平行的模式。结论-局部壁内递送阿尔法(V)β(3)靶向雷帕霉素纳米粒可抑制球囊损伤后的狭窄，而不会延迟内皮愈合。
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 alpha(v)beta(3)-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) alpha(v)beta(3)-targeted rapamycin nanoparticles, (2) alpha(v)beta(3)-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 alpha(v)beta(3)-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 alpha(v)beta(3)-targeted rapamycin nanoparticles and the 3 control groups.Conclusions-Local intramural delivery of alpha(v)beta(3)-targeted rapamycin nanoparticles inhibited stenosis without delaying endothelial healing after balloon injury.