N-Alkyl-PEI-functionalized iron oxide nanoclusters for efficient siRNA delivery.
N-Alkyl-PEI-functionalized iron oxide nanoclusters for efficient siRNA delivery.
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DOI：
10.1002/smll.201100825
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发表时间：
2011-10-04
期刊：
影响因子：
13.3
通讯作者：
Chen, Xiaoyuan
中科院分区：
文献类型：
--
作者：
Liu, Gang;Xie, Jin;Zhang, Fan;Wang, Zhiyong;Luo, Kui;Zhu, Lei;Quan, Qimeng;Niu, Gang;Lee, Seulki;Ai, Hua;Chen, Xiaoyuan
小干扰RNA（siRNA）是一种新兴的治疗方法，通过调节参与疾病进展的特定基因的表达来起作用。尽管有这些承诺，但以最小的副作用有效转运siRNA仍然是一个挑战。在这项研究中，非病毒纳米颗粒基因载体已被开发，并已在体外和体内水平验证其siRNA递送和转染的效率。这种纳米载体，缩写为烷基-PEI 2k-IO，由氧化铁（IO）的核和烷基化PEI 2000（烷基-PEI 2k）的壳构成。发现它能够与siRNA结合，从而产生具有受控簇结构和窄尺寸分布的良好分散的纳米颗粒。电泳研究表明，Alkyl-PEI 2k-IO在N/P比大于10时可以完全阻滞siRNA，保护siRNA免受血清中的酶降解，并且在聚阴离子肝素存在下有效地释放复合的siRNA。用稳定表达荧光素酶（fluc-4 T1）的4 T1细胞以及进一步用fluc-4 T1异种移植物模型评估加载siRNA的纳米载体的敲低效率。观察到荧光素酶的显著下调，并且与高分子量类似物不同，烷基-PEI 2k涂覆的IO显示出良好的生物相容性。总之，烷基-PEI 2k-IO表现出siRNA的高效递送和无害的毒性特征，使其成为基因治疗的潜在载体。
Small interfering RNA (siRNA) is an emerging class of therapeutics, working by regulating the expression of a specific gene involved in disease progression. Despite the promises, effective transport of siRNA with minimal side effects remains a challenge. In this study, a non-viral nanoparticle gene carrier has been developed and its efficiency for siRNA delivery and transfection has been validated at both in vitro and in vivo levels. Such a nanocarrier, abbreviated as Alkyl-PEI2k-IO, was constructed with a core of iron oxide (IO) and a shell of alkylated PEI2000 (Alkyl-PEI2k). It was found to be able to bind with siRNA, resulting in well-dispersed nanoparticles with a controlled clustering structure and narrow size distribution. Electrophoresis studies showed that the Alkyl-PEI2k-IOs could retard siRNA completely at N/P ratios above 10, protect siRNA from enzymatic degradation in serum and release complexed siRNA efficiently in the presence of polyanionic heparin. The knockdown efficiency of the siRNA loaded nanocarriers was assessed with 4T1 cells stably expressing luciferase (fluc-4T1) and further, with a fluc-4T1 xenograft model. Significant downregulation of luciferase was observed, and unlike the high molecular weight analogs, the Alkyl-PEI2k coated IOs showed a good biocompatibility. In conclusion, Alkyl-PEI2k-IOs demonstrate highly efficient delivery of siRNA and an innocuous toxic profile, making it a potential carrier for gene therapy.
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低分子量聚乙烯亚胺共轭金纳米粒子作为高效基因载体
影响因子：
4.7
作者：
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影响因子：
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作者：
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DOI：
10.1038/nrd2310
发表时间：
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期刊：
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影响因子：
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作者：
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影响因子：
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作者：
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