Application of nanoparticle technology for the prevention of restenosis after balloon injury in rats
Application of nanoparticle technology for the prevention of restenosis after balloon injury in rats
复制标题
DOI：
10.1161/01.res.0000069021.56380.e2
复制
发表时间：
2003-04-18
影响因子：
20.1
通讯作者：
Takeshita, A
中科院分区：
文献类型：
--
作者：
Uwatoku, T;Shimokawa, H;Takeshita, A
经皮冠状动脉介入治疗后的再狭窄仍然是临床心脏病学中的一个严重问题。纳米颗粒技术的最新进展使我们能够在更长的时间内选择性地将抗增殖药物递送到球囊损伤的动脉。 NK911是一种封装阿霉素的聚乙二醇嵌段共聚物的核壳纳米颗粒，在血管病变中积聚，渗透性增加。我们首先证实球囊损伤导致大鼠颈动脉血管通透性显着且持续增加（通过伊文思蓝染色评估）一周。然后我们观察到，在单损伤和双损伤模型中，仅静脉注射 3 次 NK911（而非单独使用阿霉素）即可在损伤后 4 周显着抑制大鼠颈动脉的新内膜形成。免疫染色表明，NK911 的作用是由于抑制血管平滑肌增殖，而不是增强细胞凋亡或抑制炎症细胞募集。对阿霉素血管浓度的测量证实，在单损伤和双损伤模型中，NK911 都能有效地将药物递送至球囊损伤的动脉。 RNA保护实验表明NK911抑制多种细胞因子的表达，但不抑制凋亡相关分子的表达。 NK911 耐受性良好，没有任何不良的全身反应。这些结果表明，以增加渗透性的方式靶向血管病变的纳米颗粒技术是预防球囊损伤后再狭窄的一种有前途且安全的方法。本文全文可在http://www. circresaha.org。
Restenosis after percutaneous coronary intervention continues to be a serious problem in clinical cardiology. Recent advances in nanoparticle technology have enabled us to deliver an antiproliferative drug selectively to the balloon-injured artery for a longer time. NK911, which is a core-shell nanoparticle of polyethyleneglycol-based block copolymer encapsulating doxorubicin, accumulates in vascular lesions with increased permeability. We first confirmed that balloon injury caused a marked and sustained increase in vascular permeability ( as evaluated by Evans blue staining) for a week in the rat carotid artery. We then observed that intravenous administration of just 3 times of NK911, but not doxorubicin alone, significantly inhibited the neointimal formation of the rat carotid artery at 4 weeks after the injury in both a single- and double-injury model. Immunostaining demonstrated that the effect of NK911 was due to inhibition of vascular smooth muscle proliferation but not to enhancement of apoptosis or inhibition of inflammatory cell recruitment. Measurement of vascular concentrations of doxorubicin confirmed the effective delivery of the agent to the balloon-injured artery by NK911 in both a single- and double-injury model. RNA protection assay demonstrated that NK911 inhibited expression of several cytokines but not that of apoptosis-related molecules. NK911 was well tolerated without any adverse systemic effects. These results suggest that nanoparticle technology to target vascular lesions with increased permeability is a promising and safe approach for the prevention of restenosis after balloon injury. The full text of this article is available at http:// www. circresaha.org.