Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
J Control Release. 2014 Nov 10;193:316-23. doi: 10.1016/j.jconrel.2014.04.023. Epub 2014 Apr 26.
We report on the development of a multifunctional envelope-type nano device (MEND) based on our packaging concept "Programmed packaging" to control not only intracellular trafficking but also the biodistribution of encapsulated compounds such as nucleic acids/proteins/peptides. Our strategy for achieving this is based on molecular mechanisms of cell biology such as endocytosis, vesicular trafficking, etc. In this review, we summarize the concept of programmed packaging and discuss some of our recent successful examples of using MENDs. Systematic evolution of ligands by exponential enrichment (SELEX) was applied as a new methodology for identifying a new ligand toward cell or mitochondria. The delivery of siRNA to tumors and the tumor vasculature was achieved using pH sensitive lipid (YSK05), which was newly designed and optimized under in vivo conditions. The efficient delivery of pDNA to immune cells such as dendritic cells has also been developed using the KALA ligand, which can be a breakthrough technology for DNA vaccine. Finally, ss-cleavable and pH-activated lipid-like surfactant (ssPalm) which is a lipid like material with pH-activatable and SS-cleavable properties is also introduced as a proof of our concept.
我们报告了一种基于我们的“编程包装”包装概念的多功能信封型纳米装置（MEND）的开发，该装置不仅可以控制细胞内运输，还可以控制封装化合物（如核酸/蛋白质/肽）的生物分布。我们实现这一目标的策略基于细胞生物学的分子机制，如内吞作用、囊泡运输等。在这篇综述中，我们总结了编程包装的概念，并讨论了我们最近使用 MEND 的一些成功例子。指数富集的配体系统进化（SELEX）被应用于鉴定针对细胞或线粒体的新配体的新方法。使用新设计和优化的 pH 敏感脂质（YSK05）将 siRNA 递送到肿瘤和肿瘤血管中。使用 KALA 配体也可以有效地将 pDNA 递送到树突状细胞等免疫细胞中，这可能是 DNA 疫苗的一项突破技术。最后，还介绍了具有 pH 激活和 ss 切割特性的 ss 可切割和 pH 激活的类脂质表面活性剂（ssPalm），作为我们概念的证明。
