title: Bioimaging of Hyaluronate-Interferon α Conjugates Using a Non-Interfering Zwitterionic Fluorophore.
abstract: We conducted real-time bioimaging of the hyaluronate-interferon α (HA-IFNα) conjugate using a biologically inert zwitterionic fluorophore of ZW800-1 for the treatment of hepatitis C virus (HCV) infection. ZW800-1 was labeled on the IFNα molecule of the HA-IFNα conjugate to investigate its biodistribution and clearance without altering its physicochemical and targeting characteristics. Confocal microscopy clearly visualized the effective in vitro cellular uptake of the HA-IFNα conjugate to HepG2 cells. After verifying the biological activity in Daudi cells, we conducted the pharmacokinetic analysis of the HA-IFNα conjugate, which confirmed its target-specific delivery to the liver with a prolonged residence time longer than that of PEGylated IFNα. In vivo and ex vivo bioimaging of the ZW800-1-labeled HA-IFNα conjugate directly showed real-time biodistribution and clearance of the conjugate that are consistent with the biological behaviors analyzed by an enzyme-linked immunosorbent assay. Furthermore, the elevated level of OAS1 mRNA in the liver confirmed in vivo antiviral activity of HA-IFNα conjugates. With the data taken together, we could confirm the feasibility of ZW800-1 as a biologically inert fluorophore and target-specific HA-IFNα conjugate for the treatment of HCV infection.
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School , 65 Landsdowne Street, Cambridge, Massachusetts 02139, United States.
authors.forename: Ki Su
authors.initials: KS
authors.lastname: Kim
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School , 330 Brookline Avenue, Boston, Massachusetts 02215, United States.|Department of Biomedical Science, Chonnam National University Medical School , 160 Baekseo-ro, Dong-gu, Gwangju 501-746, Korea.
authors.forename: Hoon
authors.initials: H
authors.lastname: Hyun
authors.affiliation: Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH) , 77 Cheongam-ro, Nam-gu, Pohang, Kyungbuk 790-784, Korea.
authors.forename: Jeong-A
authors.initials: JA
authors.lastname: Yang
authors.affiliation: Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH) , 77 Cheongam-ro, Nam-gu, Pohang, Kyungbuk 790-784, Korea.
authors.forename: Min Young
authors.initials: MY
authors.lastname: Lee
authors.affiliation: Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH) , 77 Cheongam-ro, Nam-gu, Pohang, Kyungbuk 790-784, Korea.
authors.forename: Hyemin
authors.initials: H
authors.lastname: Kim
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School , 65 Landsdowne Street, Cambridge, Massachusetts 02139, United States.
authors.forename: Seok-Hyun
authors.initials: SH
authors.lastname: Yun
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School , 330 Brookline Avenue, Boston, Massachusetts 02215, United States.
authors.forename: Hak Soo
authors.initials: HS
authors.lastname: Choi
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School , 65 Landsdowne Street, Cambridge, Massachusetts 02139, United States.|Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH) , 77 Cheongam-ro, Nam-gu, Pohang, Kyungbuk 790-784, Korea.
authors.forename: Sei Kwang
authors.initials: SK
authors.lastname: Hahn
mesh_terms: D056945:Hep G2 Cells; D016174:Hepacivirus; D006526:Hepatitis C / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology; D016898:Interferon-alpha / Q000737:chemistry / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D000644:Quaternary Ammonium Compounds / Q000737:chemistry / Q000494:pharmacology; D013451:Sulfonic Acids / Q000737:chemistry / Q000494:pharmacology
chemical_list: D016898:Interferon-alpha; D000644:Quaternary Ammonium Compounds; D013451:Sulfonic Acids; C562069:ZW800-1 compound; D006820:Hyaluronic Acid