Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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Enhanced Tumor-targeted Gene Delivery by Immunolipoplexes Conjugated with the Humanized Anti-TAG-72 Fab' Fragments

  • Kim, Keun-Sik (Department of Biomedical Laboratory Science, Konyang University) ;
  • Park, Yong-Serk (Department of Biomedical Laboratory Science, Yonsei University) ;
  • Hong, Hyo-Jeong (Department of Systems Immunology, Kangwon National University) ;
  • Kim, Kwang-Pyo (Department of Molecular Biotechnology, Konkuk University) ;
  • Lee, Kwang-Hyun (Department of Bioscience and Biotechnology, Konkuk University) ;
  • Kim, Dong-Eun (Department of Bioscience and Biotechnology, Konkuk University)
  • Received : 2012.01.06
  • Accepted : 2012.01.17
  • Published : 2012.02.20
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Abstract

Cationic immunoliposomes were prepared by conjugation of Fab' fragments of the recombinant humanized monoclonal antibody (HuCC49) against tumor-associated glycoprotein (TAG)-72 to sterically unilamella liposomes. The cationic immunoliposomes are composed of cationic lipid (O,O'-dimyristyl-N-lysyl aspartate, DMKD), cholesterol, and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide(polyethyleneglycol)$_{2000}$] (DPPE-PEG-maleimide) with a molar ratio of 0.5:0.47:0.03. Plasmid DNA was effectively condensed by addition of transferrin (Tf) during the formation of anti-TAG-72 PEG-immunolipoplexes (PILPs). These anti-TAG-72 PILPs were able to adhere to the surface of TAG-72-overexepressing LS174T human colon cancer cells more effectively than conventional liposomes, thereby facilitating gene delivery in vitro. Furthermore, intravenous administration of the anti-TAG-72 PILPs into the tumor-carrying mice exhibited efficient localization of the reporter gene in the tumor tissues.

Keywords

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