Biomedical Engineering Reference
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osmolarity inside the endosome, which eventually induce abrupt swelling and
rupture of the endosome.
Fig. 16. Proton sponge mechanism of cationic polymers in endosome.
Recently, cationic polymers such as histidylated chitosan, histidylated
poly(lysine), polyhistidine-based polymers, poly(4-vinylimidazole), and
imidazole-containing polymers have shown considerable promise as nonviral
vectors for DNA delivery, given their endosomolytic ability by imidazole
groups.[39-44] The first use of histidine-containing polymers for DNA delivery
was reported in 1998 by Midoux and coworkers [45]. Histidine-rich peptide
(H5WYG) is a variant of the HA-2 subunit of the influenza virus hemaglutin,
designed by substituting lysine with histidyl residues. This histidine-rich peptide
did not disrupt the membrane at neutral pH, but showed a powerful membrane
disruption ability at pH 6.4.
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