title: Phenylboronic acid-installed polymeric micelles for targeting sialylated epitopes in solid tumors.
abstract: Ligand-mediated targeting of nanocarriers to tumors is an attractive strategy for increasing the efficiency of chemotherapies. Sialylated glycans represent a propitious target as they are broadly overexpressed in tumor cells. Because phenylboronic acid (PBA) can selectively recognize sialic acid (SA), herein, we developed PBA-installed micellar nanocarriers incorporating the parent complex of the anticancer drug oxaliplatin, for targeting sialylated epitopes overexpressed on cancer cells. Following PBA-installation, the micelles showed high affinity for SA, as confirmed by fluorescence spectroscopy even at intratumoral pH conditions, i.e., pH 6.5, improving their cellular recognition and uptake and enhancing their in vitro cytotoxicity against B16F10 murine melanoma cells. In vivo, PBA-installed micelles effectively reduced the growth rate of both orthotopic and lung metastasis models of melanoma, suggesting the potential of PBA-installed nanocarriers for enhanced tumor targeting.
authors.affiliation: Department of Materials Engineering, ‡Department of Bioengineering, §Division of Tissue Engineering, and ∥Center for Disease Biology and Integrative Medicine, Graduate School of Engineering, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Deshayes
authors.forename: Horacio
authors.initials: H
authors.lastname: Cabral
authors.forename: Takehiko
authors.initials: T
authors.lastname: Ishii
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Miura
authors.forename: Shutaro
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamashita
authors.forename: Akira
authors.initials: A
authors.lastname: Matsumoto
authors.forename: Yuji
authors.initials: Y
authors.lastname: Miyahara
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nishiyama
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kataoka
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001897:Boronic Acids / Q000008:administration & dosage / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D000939:Epitopes / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008823:Micelles; D015394:Molecular Structure; D019158:N-Acetylneuraminic Acid / Q000737:chemistry* / Q000378:metabolism; D049329:Nanostructures / Q000737:chemistry; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D000077150:Oxaliplatin; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D004337:Drug Carriers; D000939:Epitopes; D008823:Micelles; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D019158:N-Acetylneuraminic Acid; C010686:benzeneboronic acid