title: Targeting Notch-1 positive acute leukemia cells by novel fucose-bound liposomes carrying daunorubicin.
abstract: Complete remission by induction therapy in acute myelogenous leukemia (AML) can be achieved due to improvements in supportive and optimized therapy. However, more than 20% of patients will still need to undergo salvage therapy, and most will have a poor prognosis. Determining the specificity of drugs to leukemia cells is important since this will maximize the dose of chemotherapeutic agents that can be administered to AML patients. In turn, this would be expected to lead to reduced drug toxicity and its increased efficacy. We targeted Notch-1 positive AML cells utilizing fucose-bound liposomes, since activation of Notch-1 is required for O-fucosylation. Herein, we report that intravenously injected, L-fucose-bound liposomes containing daunorubicin can be successfully delivered to AML cells that express fucosylated antigens. This resulted in efficient tumor growth inhibition in tumor-bearing mice and decreased proliferation of AML patient-derived leukemia cells. Thus, biological targeting by fucose-bound liposomes that takes advantage of the intrinsic characteristics of AML cells could be a promising new strategy for Notch-1 positive-AML treatment.
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Michihiro
authors.initials: M
authors.lastname: Ono
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.|Division of Clinical Oncology, Sapporo Medical University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Rishu
authors.initials: R
authors.lastname: Takimoto
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Osuga
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.|Division of Clinical Oncology, Sapporo Medical University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Okagawa
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hirakawa
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.|Division of Clinical Oncology, Sapporo Medical University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Arihara
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.|Division of Clinical Oncology, Sapporo Medical University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Uemura
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.|Division of Clinical Oncology, Sapporo Medical University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Hayasaka
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.|Division of Clinical Oncology, Sapporo Medical University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Miura
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.|Division of Clinical Oncology, Sapporo Medical University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Teppei
authors.initials: T
authors.lastname: Matsuno
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Fumito
authors.initials: F
authors.lastname: Tamura
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.|Division of Molecular Oncology, Sapporo Medical University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Iyama
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Miyanishi
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Kohichi
authors.initials: K
authors.lastname: Takada
authors.affiliation: Division of Molecular Oncology, Sapporo Medical University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kobune
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.|Division of Clinical Oncology, Sapporo Medical University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Kato
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology; D045744:Cell Line, Tumor; D003630:Daunorubicin / Q000008:administration & dosage*; D005260:Female; D005643:Fucose / Q000008:administration & dosage / Q000737:chemistry; D018922:HL-60 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D051379:Mice; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D051881:Receptor, Notch1 / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D055815:Young Adult
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D005643:Fucose; D003630:Daunorubicin
keywords: AML; L-fucose; Notch-1; liposome; targeting