Institute of Advanced Materials and ‡Key Laboratory for Organic Electronics and Information Displays and Institute of Advanced Materials, Nanjing University of Posts and Telecommunications , Nanjing 210046, China.
Biomacromolecules. 2013 Oct 14;14(10):3643-52. doi: 10.1021/bm401000x. Epub 2013 Sep 27.
RNA interference is supposed to be one of the most powerful technologies for suppression of genes and treatment of diverse human diseases while the safe delivery and visualization of siRNA were still challenging. In this text, a novel type of monodispersed conjugated polymer nanoparticles PFNBr with brush-like molecular structure was introduced into siRNA delivery system. The nanoparticles exhibited dual functions conveniently in the delivery system which can not only carry high amount of siRNA to penetrate intracellularly for knocking down targeted mRNA but also act as signal agents for siRNA tracking and cellular imaging. Due to the high density side chains with positive charges and more extended conformation of the spatial structure, PFNBr nanoparticles as nanocarrier for siRNA provided outstanding capture ability (1 mol polymer to more than 32.5 mol siRNA) and enhanced protection capability of siRNA molecules from degradation. Here, it should be noted that the concentration of carrier in the working platform was lowered from the level of μmol/L to nmol/L compared with other conjugated polymer delivery systems due to the outstanding carrying capacity of PFNBr. And meanwhile, this system acquired high gene silence efficiency and good biocompatibility. The proposed complex nanoparticles efficiently transfected siPlk1 into PANC-1 cells and induced high knockdown efficiency for targeted Plk1 mRNA to 23.9% and no significant cytotoxicity of the PFNBr/siRNA complexes was shown. Therefore, this working platform provides a solution to most of the common problems associated with the siRNA delivery, visualization, and therapeutic applications, and keeps a bright outlook for the development of new nucleic acid-based therapeutics and simultaneously for fluorescent bioimaging.
RNA 干扰被认为是抑制基因和治疗多种人类疾病最有效的技术之一，而 siRNA 的安全递送和可视化仍然具有挑战性。在本文中，我们引入了一种新型的单分散共轭聚合物纳米粒子 PFNBr，其具有刷状分子结构，被引入到 siRNA 递送系统中。该纳米粒子在递送系统中具有双重功能，不仅可以携带大量的 siRNA 穿透细胞内以敲低靶向 mRNA，还可以作为 siRNA 跟踪和细胞成像的信号剂。由于带有正电荷的高密度侧链和更扩展的空间结构构象，PFNBr 纳米粒子作为 siRNA 的纳米载体提供了出色的捕获能力（1 摩尔聚合物可结合超过 32.5 摩尔的 siRNA）和增强了 siRNA 分子免受降解的保护能力。这里需要注意的是，与其他共轭聚合物递送系统相比，由于 PFNBr 的出色载物能力，工作平台中载体的浓度从μmol/L 降低到了 nmol/L 。同时，该系统还获得了高基因沉默效率和良好的生物相容性。所提出的复合纳米粒子有效地将 siPlk1 转染到 PANC-1 细胞中，并诱导针对 Plk1 mRNA 的高敲低效率达到 23.9%，而 PFNBr/siRNA 复合物没有显示出明显的细胞毒性。因此，该工作平台为与 siRNA 递送、可视化和治疗应用相关的大多数常见问题提供了一种解决方案，并为新的核酸治疗方法和荧光生物成像的发展提供了广阔的前景。
