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Fab antibody fragment-functionalized liposomes for specific targeting of antigen-positive cells

A. Ohradanova-Repic, E. Nogueira, I. Hartl, AC. Gomes, A. Preto, E. Steinhuber, V. Mühlgrabner, M. Repic, M. Kuttke, A. Zwirzitz, M. Prouza, M. Suchanek, G. Wozniak-Knopp, V. Horejsi, G. Schabbauer, A. Cavaco-Paulo, H. Stockinger,

. 2018 ; 14 (1) : 123-130. [pub] 20170919

Language English Country United States

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc19001176

Liposomes functionalized with monoclonal antibodies or their antigen-binding fragments have attracted much attention as specific drug delivery devices for treatment of various diseases including cancer. The conjugation of antibodies to liposomes is usually achieved by covalent coupling using cross-linkers in a reaction that might adversely affect the characteristics of the final product. Here we present an alternative strategy for liposome functionalization: we created a recombinant Fab antibody fragment genetically fused on its C-terminus to the hydrophobic peptide derived from pulmonary surfactant protein D, which became inserted into the liposomal bilayer during liposomal preparation and anchored the Fab onto the liposome surface. The Fab-conjugated liposomes specifically recognized antigen-positive cells and efficiently delivered their cargo, the Alexa Fluor 647 dye, into target cells in vitro and in vivo. In conclusion, our approach offers the potential for straightforward development of nanomedicines functionalized with an antibody of choice without the need of harmful cross-linkers.

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$a Fab antibody fragment-functionalized liposomes for specific targeting of antigen-positive cells / $c A. Ohradanova-Repic, E. Nogueira, I. Hartl, AC. Gomes, A. Preto, E. Steinhuber, V. Mühlgrabner, M. Repic, M. Kuttke, A. Zwirzitz, M. Prouza, M. Suchanek, G. Wozniak-Knopp, V. Horejsi, G. Schabbauer, A. Cavaco-Paulo, H. Stockinger,
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$a Liposomes functionalized with monoclonal antibodies or their antigen-binding fragments have attracted much attention as specific drug delivery devices for treatment of various diseases including cancer. The conjugation of antibodies to liposomes is usually achieved by covalent coupling using cross-linkers in a reaction that might adversely affect the characteristics of the final product. Here we present an alternative strategy for liposome functionalization: we created a recombinant Fab antibody fragment genetically fused on its C-terminus to the hydrophobic peptide derived from pulmonary surfactant protein D, which became inserted into the liposomal bilayer during liposomal preparation and anchored the Fab onto the liposome surface. The Fab-conjugated liposomes specifically recognized antigen-positive cells and efficiently delivered their cargo, the Alexa Fluor 647 dye, into target cells in vitro and in vivo. In conclusion, our approach offers the potential for straightforward development of nanomedicines functionalized with an antibody of choice without the need of harmful cross-linkers.
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$a Nogueira, Eugénia $u Centre of Biological Engineering, University of Minho, Campus of Gualtar, Braga, Portugal; Centre of Molecular and Environmental Biology, Department of Biology, University of Minho, Campus of Gualtar, Braga, Portugal.
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$a Hartl, Ingrid $u Institute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
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$a Gomes, Andreia C $u Centre of Molecular and Environmental Biology, Department of Biology, University of Minho, Campus of Gualtar, Braga, Portugal.
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$a Preto, Ana $u Centre of Molecular and Environmental Biology, Department of Biology, University of Minho, Campus of Gualtar, Braga, Portugal.
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$a Steinhuber, Eva $u Institute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
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$a Mühlgrabner, Vanessa $u Institute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
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$a Repic, Marko $u MC Toxicology Consulting, Vienna, Austria.
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$a Kuttke, Mario $u Institute for Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
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$a Zwirzitz, Alexander $u Institute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
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$a Prouza, Marek $u EXBIO Praha, Vestec, Czech Republic.
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$a Suchanek, Miloslav $u EXBIO Praha, Vestec, Czech Republic.
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$a Wozniak-Knopp, Gordana $u Christian Doppler Laboratory for Innovative Immunotherapeutics, Department of Biotechnology, University of Natural Resources and Life Sciences (BOKU), Vienna, Austria.
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$a Horejsi, Vaclav $u Institute of Molecular Genetics of the Academy of Sciences of the Czech Republic, Prague, Czech Republic.
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$a Schabbauer, Gernot $u Institute for Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
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$a Cavaco-Paulo, Artur $u Centre of Biological Engineering, University of Minho, Campus of Gualtar, Braga, Portugal.
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$a Stockinger, Hannes $u Institute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
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