TY - JOUR
T1 - Fab antibody fragment-functionalized liposomes for specific targeting of antigen-positive cells
AU - Ohradanova-Repic, A.
AU - Nogueira, E.
AU - Hartl, I.
AU - Gomes, A.C.
AU - Preto, A.
AU - Steinhuber, E.
AU - Mühlgrabner, V.
AU - Repic, M.
AU - Kuttke, M.
AU - Zwirzitz, A.
AU - Prouza, M.
AU - Suchanek, M.
AU - Wozniak-Knopp, G.
AU - Horejsi, V.
AU - Schabbauer, G.
AU - Cavaco-Paulo, A.
AU - Stockinger, H.
N1 - Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2018/1
Y1 - 2018/1
N2 - 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.
AB - 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.
KW - Active targeting
KW - Antibody engineering
KW - Immunoliposome
KW - Liposome functionalization
KW - Recombinant Fab antibody fragment
UR - http://www.scopus.com/inward/record.url?scp=85033370033&partnerID=8YFLogxK
U2 - 10.1016/j.nano.2017.09.003
DO - 10.1016/j.nano.2017.09.003
M3 - Article
SN - 1549-9634
VL - 14
SP - 123
EP - 130
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
IS - 1
ER -