Cationic derivatives of biocompatible hyaluronic acids for delivery of siRNA and antisense oligonucleotides
Cationic derivatives of biocompatible hyaluronic acids for delivery of siRNA and antisense oligonucleotides
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DOI：
10.1080/10611860802472461
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发表时间：
2009-02-01
影响因子：
4.5
通讯作者：
Oh, Yu-Kyoung
中科院分区：
文献类型：
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作者：
Han, Su-Eun;Kang, Hyungu;Oh, Yu-Kyoung
在这项研究中，我们测试了使用生物相容性透明质酸（HA）的阳离子聚合物衍生物作为siRNA和反义寡核苷酸的递送系统。用阳离子聚合物聚乙烯亚胺（PEI）对HA进行改性。当与单独的PEI相比时，HA的阳离子PEI衍生物（HA-PEI）在B16 F1、A549、HeLa和Hep 3B肿瘤细胞中提供增加的小干扰RNA（siRNA）的细胞递送。事实上，在用HA-PEI递送siRNA后，超过95%的细胞对siRNA呈阳性。使用HA-PEI递送的存活素特异性siRNA有效地降低了所有细胞系中靶基因的mRNA表达水平。相比之下，单独由PEI递送的存活素特异性siRNA不诱导mRNA水平的显著降低。在表达绿色荧光蛋白（GFP）的293 T细胞中，GFP表达的丧失在已经用GFP特异性siRNA和HA-PEI复合物处理的细胞中是明显的。反义寡核苷酸63139对靶基因表达的抑制作用在与HA-PEI一起递送后也增强。此外，HA-PEI显示出比单独的PEI更低的细胞毒性。这些结果表明，HA-PEI可以进一步开发为siRNA和反义寡核苷酸的生物相容性递送系统，用于增强细胞摄取和抑制靶基因表达。
In this study, we tested the use of cationic polymer derivatives of biocompatible hyaluronic acid (HA) as a delivery system of siRNA and antisense oligonucleotides. HA was modified with cationic polymer polyethylenimine (PEI). When compared with PEI alone, cationic PEI derivatives of HA (HA-PEI) provided increased cellular delivery of Small interfering RNA (siRNA) in B16F1, A549, HeLa, and Hep3B tumor cells. Indeed, more than 95% of the cells were positive for siRNA following its delivery with HA-PEI. A survivin-specific siRNA that was delivered using HA-PEI potently reduced the mRNA expression levels of the target gene in all of the cell lines. By contrast, survivin-specific siRNA delivered by PEI alone did not induce a significant reduction in mRNA levels. In green fluorescent protein (GFP)-expressing 293 T cells, a loss of GFP expression was evident in the cells that had been treated with GFP-specific siRNA and HA-PEI complex. The inhibition of target gene expression by antisense oligonucleotide 63139 was also enhanced after delivery with HA-PEI. Moreover, HA-PEI displayed lower cytotoxicity than PEI alone. These results suggest that HA-PEI could be further developed as biocompatible delivery systems of siRNA and antisense oligonucleotides for enhanced cellular uptake and inhibition of target gene expression.