Organic-inorganic hybrid-nanocarrier of siRNA constructing through the self-assembly of calcium phosphate and PEG-based block aniomer
Organic-inorganic hybrid-nanocarrier of siRNA constructing through the self-assembly of calcium phosphate and PEG-based block aniomer
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DOI：
10.1016/j.jconrel.2006.01.004
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发表时间：
2006-04-10
影响因子：
10.8
通讯作者：
Kataoka, K
中科院分区：
文献类型：
--
作者：
Kakizawa, Y;Furukawa, S;Kataoka, K
SiRNA递送系统的开发是实用的RNA疗法的关键，该疗法有望治疗危及生命的人类疾病，但由于高转染率、在生物介质中的耐受性和低毒性等各种要求，其构建仍然存在巨大的困难。本文报道了一种新型的包埋siRNA的有机-无机杂化纳米载体的制备方法，该方法是基于聚乙二醇聚甲基丙烯酸嵌段与磷酸钙晶体的自组装。纳米载体的直径在数百纳米范围内，由于聚乙二醇栅的空间稳定作用，显示出优异的胶体稳定性。利用稳定表达荧光素酶基因的293细胞对负载在纳米载体中的siRNA的生物学活性进行了检测，结果表明，在不使用任何佐剂分子如铬喹的情况下，siRNA具有非常高的基因沉默效率。该系统的另一个优点是血清耐受性，这是体内应用中的一个关键问题。(C)2006爱思唯尔B.V.保留所有权利。
The development of siRNA delivery systems is a major key for practical RNA therapy that holds promise for the treatment of life-threatening human diseases, yet there still exists significant difficulties in their construction because of the various requirements including high transfection efficacy, tolerability in the biological medium, and low toxicity. Here we report the novel preparation route of organic-inorganic hybrid-nanocarriers entrapping siRNA based on the self-assembly of the block aniomer, poly(ethylene glycol)-block-poly(methacrylic acid), with calcium phosphate crystals. The nanocarriers; have diameters in the range of several hundreds of nanometers and revealed excellent colloidal stability due to the steric stabilization effect of the PEG palisade. The biological activity of siRNA loaded in nanocarriers was assessed using 293 cells stably expressing luciferase gene, showing the remarkably high gene silencing-efficacy without the use of any adjuvant molecules such as chroloquin. Further advantage of the system is the serum tolerability, which is of a critical issue in in vivo application. (c) 2006 Elsevier B.V. All rights reserved.