title: Efficient and High-Speed Transduction of an Antibody into Living Cells Using a Multifunctional Nanocarrier System to Control Intracellular Trafficking.
abstract: The transduction of antibodies into living cells would represent a major contribution to both basic and applied biomedical fields, as currently available methods suffer from limitations such as low-uptake efficiency and endosomal entrapment. In this study, a liposome-based carrier was designed to overcome these issues. Liposomes were modified with octaarginine (R8), a cell penetrating peptide and GALA, a pH-sensitive fusogenic peptide. The presence of R8 enhanced the cellular uptake of antibodies, whereas GALA reduced endosomal entrapment, resulting in antibodies being released into the cytosol within 30 min. Moreover, compared with commercially available reagents for delivering antibodies, our system was superior in both cellular uptake and endosomal escape. In addition, specific antibodies delivered by R8-GALA liposomes were found to be associated with their epitope, confirming the preservation of functionality. This system for the efficient and high-speed cytosolic delivery of an antibody provides a valuable tool that can be useful in basic and applied research for analyzing the expression and function of intracellular molecules.
authors.affiliation: Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, 060-0812, Japan.
authors.forename: Yuma
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, 060-0812, Japan.
authors.forename: Sandra Milena Vergara
authors.initials: SM
authors.lastname: Perez
authors.affiliation: Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, 060-0812, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Tabata
authors.affiliation: Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, 060-0812, Japan.|Department of Pediatrics, Hokkaido University Hospital, Sapporo, 060-8638, Japan.
authors.forename: Jiro
authors.initials: J
authors.lastname: Abe
authors.affiliation: Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, 060-0812, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Yasuzaki
authors.affiliation: Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, 060-0812, Japan.
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Harashima
mesh_terms: D000906:Antibodies / Q000378:metabolism*; D000918:Antibody Specificity; D003600:Cytosol / Q000378:metabolism; D004337:Drug Carriers / Q000494:pharmacology*; D016503:Drug Delivery Systems; D011992:Endosomes / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008081:Liposomes; D049329:Nanostructures; D009842:Oligopeptides / Q000737:chemistry; D010455:Peptides / Q000737:chemistry
chemical_list: D000906:Antibodies; D004337:Drug Carriers; D008081:Liposomes; D009842:Oligopeptides; D010455:Peptides; C448619:octaarginine; C066951:GALA peptide
keywords: GALA; antibody delivery; antibody drug; biomaterials; liposomes; macromolecular drug delivery; multifunctional envelope-type nano device (MEND); nanoparticles; octaarginine; protein delivery