Bioimaging of Hyaluronate鈥揑nterferon 伪 Conjugates Using a Non-Interfering Zwitterionic Fluorophore

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• 作者：Ki Su Kim ; Hoon Hyun ; Jeong-A Yang ; Min Young Lee ; Hyemin Kim ; Seok-Hyun Yun ; Hak Soo Choi ; Sei Kwang Hahn
• 刊名：Biomacromolecules
• 出版年：2015
• 出版时间：September 14, 2015
• 年：2015
• 卷：16
• 期：9
• 页码：3054-3061
• 全文大小：560K
• ISSN：1526-4602

文摘

We conducted real-time bioimaging of the hyaluronate鈥搃nterferon 伪 (HA鈥揑FN伪) 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 IFN伪 molecule of the HA鈥揑FN伪 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鈥揑FN伪 conjugate to HepG2 cells. After verifying the biological activity in Daudi cells, we conducted the pharmacokinetic analysis of the HA鈥揑FN伪 conjugate, which confirmed its target-specific delivery to the liver with a prolonged residence time longer than that of PEGylated IFN伪. In vivo and ex vivo bioimaging of the ZW800-1-labeled HA鈥揑FN伪 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鈥揑FN伪 conjugates. With the data taken together, we could confirm the feasibility of ZW800-1 as a biologically inert fluorophore and target-specific HA鈥揑FN伪 conjugate for the treatment of HCV infection.