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 β‐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,HN red ‐virosomes containing HN whose disulfide bonds were irreversibly reduced (HN red ). 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.