Targeting Notch-1 positive acute leukemia cells by novel fucose-bound liposomes carrying daunorubicin

Abstract

// Michihiro Ono 1, * , Rishu Takimoto 1, 2, * , Takahiro Osuga 1 , Yutaka Okagawa 1, 2 , Masahiro Hirakawa 1 , Makoto Yoshida 1 , Yohei Arihara 1, 2 , Naoki Uemura 1, 2 , Naoki Hayasaka 1, 2 , Shogo Miura 1, 2 , Teppei Matsuno 1, 2 , Fumito Tamura 1 Yasushi Sato 1 , Tsutomu Sato 1, 3 , Satoshi Iyama 1 , Koji Miyanishi 1 , Kohichi Takada 1 , Masayoshi Kobune 3 , Junji Kato 1, 2 1 Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan 2 Division of Clinical Oncology, Sapporo Medical University Graduate School of Medicine, Sapporo, Japan 3 Division of Molecular Oncology, Sapporo Medical University Graduate School of Medicine, Sapporo, Japan * These authors have contributed equally to this work Correspondence to: Junji Kato, email: jkato@sapmed.ac.jp Keywords: AML, Notch-1, targeting, liposome, L-fucose Received: August 25, 2015      Accepted: May 06, 2016      Published: May 23, 2016 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.