Faculty of Pharmaceutical Sciences, Hokkaido University, Japan.
Faculty of Pharmaceutical Sciences, Hokkaido University, Japan.
J Control Release. 2014 Sep 28;190:593-606. doi: 10.1016/j.jconrel.2014.03.058. Epub 2014 Apr 30.
Nanomedicine is expected to be a basic technology for using nucleic acids as a drug, in which treating the cause of diseases represent the ultimate therapy. However, a sophisticated delivery system is required for efficient delivery of RNA/DNA, since these compounds need precise control of intracellular trafficking as well as biodistribution. Here we report on the use of a multifunctional envelope-type nano device (MEND) which is capable of intracellular trafficking such as endosomal escape, delivery to mitochondria, as well as active targeting to selective tissues/cells in vivo. In this review, we focused on the controlled intracellular trafficking of antigens for advanced immunotherapy, and then introduced a mitochondrial delivery system as an organelle targeting system for unmet medical needs. We also provide a successful in vivo delivery of siRNA to the liver based on a newly designed pH-responsive cationic lipid. Finally we will discuss an important role of an active targeting system using a peptide ligand to adipose vasculature. These progresses in drug delivery system will break through the barriers exist in our body, tissues and cells and open a window for future Nanomedicine.
纳米医学有望成为将核酸用作药物的一项基本技术,其中针对病因的治疗代表着终极疗法。然而,由于这些化合物需要对细胞内运输以及生物分布进行精确控制,因此需要一种复杂的递药系统来实现 RNA/DNA 的高效递送。在这里,我们报告了一种多功能信封型纳米器件(MEND)的应用,该器件能够实现细胞内运输,如内体逃逸、递送至线粒体以及在体内对选择性组织/细胞进行主动靶向。在这篇综述中,我们重点介绍了针对先进免疫疗法的抗原的受控细胞内运输,然后介绍了一种作为细胞器靶向系统的线粒体递药系统,用于满足未满足的医疗需求。我们还提供了一种基于新设计的 pH 响应性阳离子脂质的成功将 siRNA 递送至肝脏的体内实例。最后,我们将讨论使用肽配体对脂肪血管进行主动靶向系统的重要作用。这些药物递释系统的进展将突破我们体内、组织和细胞中存在的障碍,为未来的纳米医学开辟一扇窗户。