Targeting influenza virosomes to ovarian carcinoma cells.
Reconstituted influenza virus envelopes (virosomes) containing the viral hemagglutinin (HA) have attracted attention as delivery vesicles for cytosolic drug delivery as they possess membrane fusion activity. Here, we show that influenza virosomes can be targeted towards ovarian carcinoma cells (OVCAR-3) with preservation of fusion activity. This was achieved by incorporating poly(ethylene glycol) (PEG)-derivatized lipids into the virosome membrane. This PEG layer serves as shield to prevent interaction of HA with ubiquitous sialic acid residues and as spatial anchor for antibody attachment. Coupling of Fab' fragments of mAb 323/A3 (anti-epithelial glycoprotein-2) to the distal ends of PEG lipids resulted in specific binding of virosomes to OVCAR-3 cells. These antibody-redirected virosomes fused with membranes of OVCAR-3 cells in a pH-dependent fashion.
Mastrobattista
E
E
Utrecht Institute for Pharmaceutical Sciences, Department of Pharmaceutics, Utrecht University, The Netherlands. e.mastrobattista@pharm.uu.nl
Schoen
P
P
Wilschut
J
J
Crommelin
D J
DJ
Storm
G
G
D002462:Cell Membrane / Q000378:metabolism / Q000821:virology; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D018014:Gene Transfer Techniques; D006388:Hemagglutinins / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009975:Orthomyxoviridae / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000821:virology*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000378:metabolism; D011485:Protein Binding; D013997:Time Factors; D014407:Tumor Cells, Cultured; D022701:Virosomes / Q000235:genetics*
D006388:Hemagglutinins; D022701:Virosomes; D011092:Polyethylene Glycols