Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Republic of Korea.
J Control Release. 2012 Sep 10;162(2):407-13. doi: 10.1016/j.jconrel.2012.07.006. Epub 2012 Jul 16.
Recently, small interfering RNA (siRNA) has received much attention for therapeutic applications; however, low transfection efficiency and intrinsic instability limit effective gene silencing. Here we show a new approach based on the incorporation of siRNA/polyelectrolyte complexes into biodegradable poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles to stabilize siRNA within a hydrophobic solid matrix for prolonged gene silencing. To solubilize siRNA in organic media, chitosan oligosaccharides grafted with deoxycholic acids are synthesized and complexed with siRNA, generating a self-assembled polyelectrolyte complex of 123.9 ± 56.8 nm in diameter. The complex is mixed with PLGA solution and emulsified in water to prepare siRNA-loaded PLGA nanoparticles having a diameter of about 230 nm. The excellent structural stability of the prepared nanoparticles leads to efficient cellular uptake followed by effective gene silencing even in the presence of serum proteins. These results suggest that the encapsulation of siRNA into biodegradable polymer matrix can be an effective means of improving the structural stability of siRNA for prolonged therapeutic efficacy.
最近，小干扰 RNA（siRNA）因其治疗应用而受到广泛关注；然而，低转染效率和固有不稳定性限制了有效的基因沉默。在这里，我们展示了一种新的方法，即将 siRNA/聚电解质复合物掺入可生物降解的聚（D，L-丙交酯-共-乙交酯）（PLGA）纳米粒中，以将 siRNA 稳定在疏水性固体基质中，从而实现长时间的基因沉默。为了在有机介质中溶解 siRNA，合成了接枝去氧胆酸的壳聚糖寡糖，并将其与 siRNA 复合，生成直径为 123.9 ± 56.8nm 的自组装聚电解质复合物。将该复合物与 PLGA 溶液混合，并在水中乳化，制备直径约为 230nm 的负载 siRNA 的 PLGA 纳米粒。所制备的纳米粒具有优异的结构稳定性，可有效被细胞摄取，并在存在血清蛋白的情况下有效进行基因沉默。这些结果表明，将 siRNA 包封在可生物降解的聚合物基质中可能是提高 siRNA 结构稳定性以实现长时间治疗效果的有效手段。
