title: Multifunctional envelope-type nano device for controlled intracellular trafficking and selective targeting in vivo.
abstract: 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.
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Kajimoto
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Japan.
authors.forename: Yuma
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Japan. Electronic address: harasima@pharm.hokudai.ac.jp.
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Harashima
mesh_terms: D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007167:Immunotherapy; D042541:Intracellular Space / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D050997:Nanomedicine; D049329:Nanostructures / Q000737:chemistry; D009369:Neoplasms / Q000628:therapy*; D034741:RNA, Small Interfering / Q000008:administration & dosage*
chemical_list: D034741:RNA, Small Interfering
keywords: Active targeting; Endosomal escape; In vivo siRNA delivery; Intracellular trafficking; Non-viral vector; Organelle targeting to mitochondria