Targeted delivery of hygromycin B using reconstituted Sendai viral envelopes lacking hemagglutinin-neuraminidase.
Hygromycin B was encapsulated in reconstituted Sendai viral envelopes containing only the fusion (F) protein (F-virosomes). Incubation of loaded F-virosomes with cultured HepG2 cells resulted in fusion mediated delivery of hygromycin B to the cell cytoplasm, as was inferred from inhibition of DNA synthesis. Binding of the F-virosomes to HepG2 cells was mediated by the interaction of terminal beta-galactose residues of fusion protein with asialoglycoprotein receptor on HepG2 cells, subsequently leading to fusion between the two membranes. The cytotoxic effect of hygromycin B enclosed in F-virosomes was comparable with that of F,HN-virosomes containing both hemagglutinin-neuraminidase (HN) and F protein and F,HNred-virosomes containing HN whose disulfide bonds were irreversibly reduced (HNred). Hygromycin B loaded fusogenic liposomes were prepared by coreconstituting the viral envelope containing only fusion protein with exogenous lipids. These fusogenic liposomes were found to be more active than F-virosomes at the same fusion protein concentrations.
Department of Biochemistry, University of Delhi South Campus, New Delhi, India.
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Bagai
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Sarkar
D006528:Carcinoma, Hepatocellular / Q000648:ultrastructure; D002462:Cell Membrane / Q000502:physiology; D003593:Cytoplasm / Q000378:metabolism / Q000648:ultrastructure; D004337:Drug Carriers; D015707:HN Protein; D006801:Humans; D006921:Hygromycin B / Q000008:administration & dosage*; D008081:Liposomes; D008113:Liver Neoplasms; D008561:Membrane Fusion; D010222:Parainfluenza Virus 1, Human / Q000201:enzymology / Q000648:ultrastructure*; D014407:Tumor Cells, Cultured; D014760:Viral Fusion Proteins / Q000502:physiology
D004337:Drug Carriers; D015707:HN Protein; D008081:Liposomes; D014760:Viral Fusion Proteins; D006921:Hygromycin B