Novel PDGFβR antisense encapsulated in polymeric nanospheres for the treatment of restenosis
Novel PDGFβR antisense encapsulated in polymeric nanospheres for the treatment of restenosis
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DOI：
10.1038/sj.gt.3301830
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发表时间：
2002-12-01
期刊：
影响因子：
5.1
通讯作者：
Golomb, G
中科院分区：
文献类型：
--
作者：
Cohen-Sacks, H;Najajreh, Y;Golomb, G
由生物相容性和生物可降解聚合物聚 -DL - 丙交酯/乙交酯组成且含有血小板衍生生长因子β受体反义核酸（PDGFβR - AS）的纳米球已被制备出来，并在球囊损伤大鼠再狭窄模型中进行了体内和体外研究。大小分布均匀的纳米球（约300纳米）表现出较高的包封率（81%），并且能持续释放（硫代磷酸化的）PDGFβR - AS。可以观察到细胞内化现象，以及对平滑肌细胞的抑制作用。发现部分硫代磷酸化的反义序列比完全硫代磷酸化的类似物更具特异性。在大鼠体内颈动脉模型中观察到裸反义序列和反义核酸 - 纳米颗粒（AS - NP）具有显著的抗再狭窄作用。注射反义核酸 - 纳米颗粒14天后，以管腔狭窄百分比衡量的平均新生内膜形成程度为32.21±4.75%，而空白纳米颗粒组和生理盐水纳米颗粒组分别为54.89±8.84%和53.84±5.58%。结论是，含有硫代磷酸化寡脱氧核苷酸反义核酸的聚丙交酯 - 乙交酯纳米球可作为治疗再狭窄的有效基因传递系统。
Nanospheres composed of the biocompatible and biodegradable polymer, poly-DL-lactide/glycolide and containing platelet-derived growth factor beta-receptor antisense (PDGFbetaR-AS) have been formulated and examined in vitro and in vivo in balloon-injured rat restenosis model. The nanospheres (similar to300 nm) of homogenous size distribution exhibited high encapsulation efficiency (81%), and a sustained release of PDGFbetaR-AS (phosphorothioated). Cell internalization was visualized, and the inhibitory effect on SMC was observed. Partially phosphorothioated antisense sequences were found to be more specific than the fully phosphorothioated analogs. A significant antirestenotic effect of the naked AS sequence and the AS-NP (nanoparticles) was observed in the rat carotid in vivo model. The extent of mean neointimal formation 14 days after injection of AS-NP, measured as a percentage of luminal stenosis, was 32.21 +/- 4.75% in comparison to 54.89 +/- 8.84 and 53.84 +/- 5.58% in the blank-NP and SC-NP groups, respectively. It is concluded that PLGA nanospheres containing phosphorothioated oligodeoxynucleotide antisense could serve as an effective gene delivery systems for the treatment of restenosis.