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Delivery of siRNA using siRNA/cationic vector complexes encapsulated in dendrimer-like polymeric DNAs

机译：使用封装在树枝状聚合物样聚合物DNA中的siRNA /阳离子载体复合物递送siRNA

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摘要

Small interfering RNA (siRNA) is a powerful gene silencing tool and has been considered a potential agent for the treatment of many diseases. However, development of safe and effective siRNA delivery systems still remains a great challenge. In this study, we developed a new siRNA delivery system based on the electrostatic encapsulation of siRNA/cationic vector complexes with dendrimer-like polymeric DNAs (YY-DNAs). The binary complexes of siRNA with cationic vectors such as lipofectamine (LP), polyethylenimine (PEI) and poly-L-lysine (PLL) were first constructed. Then, the encapsulation was performed by the addition of YY-DNAs to the binary complexes in order to form stable complexes of siRNA/LP/YY-DNAs, siRNA/PEI/YY-DNAs and siRNA/PLL/YY-DNAs. The encapsulated siRNA complexes showed nearly spherical morphology with about 13-37 nm average hydrodynamic size and their z-potentials were negative. The cationic complexes of siRNA/LP, siRNA/PEI and siRNA/PLL showed a high cytotoxicity towards the cells and strong aggregation with erythrocytes, while their encapsulation into YY-DNAs dramatically decreased the toxicities of complexes. Furthermore, these anionic encapsulated siRNA complexes were highly taken up by the HeLa cells and showed extremely high cellular uptake efficiencies and gene silencing effects without such cytotoxicity and aggregation. The stability of these complexes in 10% FBS and human serum was investigated and they showed high stability even after incubation for 72 h and 48 h, respectively. Therefore, we have newly identified safe and efficient anionic complexes of siRNA for clinical uses.
机译：小干扰RNA（siRNA）是一种强大的基因沉默工具，被认为是治疗许多疾病的潜在代理人。然而，安全和有效的siRNA交付系统的开发仍然是一个巨大的挑战。在这项研究中，我们开发了一种基于用树枝状聚合物样聚合物DNA（YY-DNA）的SiRNA /阳离子载体复合物的静电封装的新SiRNA递送系统。首先构建脂素（LP），聚乙胺（PEI）和聚-L-赖氨酸（PLL）如阳离子载体的siRNA的二元络合物。然后，通过向二元络合物添加YY-DNA来进行封装，以形成siRNA / LP / YY-DNA，siRNA / PEI / YY-DNA和siRNA / PLL / YY-DNA的稳定复合物。包封的siRNA复合物显示出几乎球形的形态，具有约13-37nm的平均水动力尺寸，并且它们的Z电位是阴性的。 siRNA / LP，siRNA / PEI和siRNA / PLL的阳离子复合物向细胞显示出高细胞毒性，并用红细胞的强聚集，而它们对YY-DNA的包封显着降低了复合物的毒性。此外，这些阴离子包封的siRNA复合物受到HELA细胞的高度占据，并显示出极高的细胞摄取效率和基因沉默效果，没有这种细胞毒性和聚集。研究了这些配合物在10％FBS和人血清中的稳定性，即使在孵育72小时和48小时后，它们也表现出高稳定性。因此，我们对临床用途进行了新鉴定了SiRNA的安全和有效的阴离子复合物。

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  • 来源
    《RSC Advances》 |2015年第41期|共11页
  • 作者

    El-Mahdy Ahmed F. M.; Shibata Takayuki; Kabashima Tsutomu; Zhu Qinchang; Kai Masaaki;

  • 作者单位

    Nagasaki Univ Grad Sch Biomed Sci Fac Pharmaceut Sci Nagasaki 8528521 Japan;

    Nagasaki Univ Grad Sch Biomed Sci Fac Pharmaceut Sci Nagasaki 8528521 Japan;

    Nagasaki Univ Grad Sch Biomed Sci Fac Pharmaceut Sci Nagasaki 8528521 Japan;

    Nagasaki Univ Grad Sch Biomed Sci Fac Pharmaceut Sci Nagasaki 8528521 Japan;

    Nagasaki Univ Grad Sch Biomed Sci Fac Pharmaceut Sci Nagasaki 8528521 Japan;

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  • 正文语种 eng
  • 中图分类 化学;
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