title: Lipid envelope-type nanoparticle incorporating a multifunctional peptide for systemic siRNA delivery to the pulmonary endothelium.
abstract: A system that permits the delivery of cargoes to the lung endothelium would be extraordinarily useful in terms of curing a wide variety of lung-related diseases. This study describes the development of a multifunctional envelope-type nanodevice (MEND) that targets the lung endothelium, delivers its encapsulated siRNA to the cytoplasm, and eradicates lung metastasis. The key to the success can be attributed to the presence of a surface-modified GALA peptide that has dual functions: targeting the sialic acid-terminated sugar chains on the pulmonary endothelium and subsequently delivering the encapsulated cargoes to the cytosol via endosomal membrane fusion, analogous to the influenza virus. The active targeting of MENDs without the formation of large aggregates was verified by intravital real-time confocal laser scanning microscopy in living lung tissue. The GALA-modified MEND is a promising carrier that opens a new generation of therapeutic approaches for satisfying unmet medical needs in curing lung diseases.
authors.affiliation: Laboratory for Formulation Research, Taiho Pharmaceutical Co., Ltd. , 224-2 Ebisuno, Hiraishi, Kawauchi-cho, Tokushima 771-0194, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kusumoto
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Akita
authors.forename: Taichi
authors.initials: T
authors.lastname: Ishitsuka
authors.forename: Yu
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nomoto
authors.forename: Ryo
authors.initials: R
authors.lastname: Furukawa
authors.forename: Ayman
authors.initials: A
authors.lastname: El-Sayed
authors.forename: Hiroto
authors.initials: H
authors.lastname: Hatakeyama
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Kajimoto
authors.forename: Yuma
authors.initials: Y
authors.lastname: Yamada
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kataoka
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Harashima
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D020868:Gene Silencing; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary* / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics*; D014162:Transfection / Q000379:methods; D016896:Treatment Outcome
chemical_list: D057846:Cell-Penetrating Peptides; D008055:Lipids; D008081:Liposomes; D053769:Nanocapsules; D034741:RNA, Small Interfering