It is anticipated that nucleic acid medicines will be in widespread use in the future, since they have the potential to cure diseases based on molecular mechanisms at the level of gene expression. However, intelligent delivery systems are required to achieve nucleic acid therapy, since they can perform their function only when they reach the intracellular site of action. We have been developing a multifunctional envelope-type nanodevice abbreviated as MEND, which consists of functional nucleic acids as a core and lipid envelope, and can control not only biodistribution but also the intracellular trafficking of nucleic acids. In this chapter, we review the development and evolution of the MEND by providing several successful examples, including the R8-MEND, the KALA-MEND, the MITO-Porter, the YSK-MEND, and the PALM.
Keywords: A multifunctional envelope-type nanodevice (MEND); Intracellular trafficking; KALA; MITO-Poter; Mitochondrial targeting; Nuclear targeting; Octaarginine (R8); Proton-activated lipid-like material (PALM); YSK; pH-sensitive cationic lipid.