Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Republic of Korea.
Biomaterials. 2013 Mar;34(9):2370-9. doi: 10.1016/j.biomaterials.2012.12.004. Epub 2013 Jan 5.
Small interfering RNA (siRNA) has been considered as a very attractive therapeutic alternative to chemical drugs; however, the chemical and biological instability and poor delivery efficiency of siRNA limit its success in clinical applications. Here we report a protein-resistant, reductively dissociable siRNA delivery system based on self-assembled polyelectrolyte complexes of dextran-siRNA conjugates linked by disulfide bonds. The prepared polyplexes exhibit excellent dispersion stability in the presence of serum because of the anti-fouling property of dextran exposed onto the complex surface. The enzymatic degradation of siRNA is also effectively suppressed within the complex. Folates are introduced as an active tumor-targeting moiety via the conjugation of folates to the hydroxyl groups of dextran. An in vivo investigation with a xenograft tumor mouse model shows that the folate-decorated dextran-siRNA conjugates are very efficiently targeted to cancer cells and induce sequence-specific gene silencing.
小干扰 RNA（siRNA）被认为是一种非常有吸引力的化学药物治疗替代物；然而，siRNA 的化学和生物不稳定性以及较差的递送效率限制了其在临床应用中的成功。在这里，我们报告了一种基于通过二硫键连接的葡聚糖-siRNA 缀合物自组装而成的聚合物电解质复合物的抗蛋白、可还原解离的 siRNA 递送系统。由于暴露在复合物表面上的葡聚糖的抗污性质，所制备的聚集体在存在血清的情况下表现出优异的分散稳定性。siRNA 的酶降解也在复合物内得到有效抑制。通过将叶酸缀合到葡聚糖的羟基上，将叶酸作为活性肿瘤靶向部分引入。用异种移植肿瘤小鼠模型进行的体内研究表明，叶酸修饰的葡聚糖-siRNA 缀合物能够非常有效地靶向癌细胞并诱导序列特异性基因沉默。
