title: Rapid Endolysosomal Escape and Controlled Intracellular Trafficking of Cell Surface Mimetic Quantum-Dots-Anchored Peptides and Glycopeptides.
abstract: A novel strategy for the development of a high performance nanoparticules platform was established by means of cell surface mimetic quantum-dots (QDs)-anchored peptides/glycopeptides, which was developed as a model system for nanoparticle-based drug delivery (NDD) vehicles with defined functions helping the specific intracellular trafficking after initial endocytosis. In this paper, we proposed a standardized protocol for the preparation of multifunctional QDs that allows for efficient cellular uptake and rapid escaping from the endolysosomal system and subsequent cytoplasmic molecular delivery to the target cellular compartment. Chemoselective ligation of the ketone-functionalized hexahistidine derivative facilitated both efficient endocytic entry and rapid endolysosomal escape of the aminooxy/phosphorylcholine self-assembled monolayer-coated QDs (AO/PCSAM-QDs) to the cytosol in various cell lines such as human normal and cancer cells, while modifications of these QDs with cell-penetrating arginine-rich peptides showed poor cellular uptake and induced self-aggregation of AO/PCSAM-QDs. Combined use of hexahistidylated AO/PCSAM-QDs with serglycine-like glycopeptides, namely synthetic proteoglycan initiators (PGIs), elicited the entry and controlled intracellular trafficking, Golgi localization, and also excretion of these nanoparticles, which suggested that the present approach would provide an ideal platform for the design of high performance NDD systems.
authors.affiliation: Faculty of Advanced Life Science and Graduate School of Life Science, Hokkaido University , N21, W11, Kita-ku, Sapporo 001-0021, Japan.
authors.forename: Roger S
authors.initials: RS
authors.lastname: Tan
authors.affiliation: Medicinal Chemistry Pharmaceuticals Co., Ltd. , N21, W12, Kita-ku, Sapporo 001-0021, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Naruchi
authors.affiliation: Faculty of Advanced Life Science and Graduate School of Life Science, Hokkaido University , N21, W11, Kita-ku, Sapporo 001-0021, Japan.
authors.forename: Maho
authors.initials: M
authors.lastname: Amano
authors.affiliation: Faculty of Advanced Life Science and Graduate School of Life Science, Hokkaido University , N21, W11, Kita-ku, Sapporo 001-0021, Japan.|Medicinal Chemistry Pharmaceuticals Co., Ltd. , N21, W12, Kita-ku, Sapporo 001-0021, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hinou
authors.affiliation: Faculty of Advanced Life Science and Graduate School of Life Science, Hokkaido University , N21, W11, Kita-ku, Sapporo 001-0021, Japan.|Medicinal Chemistry Pharmaceuticals Co., Ltd. , N21, W12, Kita-ku, Sapporo 001-0021, Japan.
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Nishimura
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000737:chemistry* / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D004705:Endocytosis; D006020:Glycopeptides / Q000737:chemistry* / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006639:Histidine / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D045663:Quantum Dots / Q000737:chemistry* / Q000378:metabolism
chemical_list: D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D006020:Glycopeptides; C471213:His-His-His-His-His-His; D009842:Oligopeptides; D006639:Histidine