Biophysical Properties
and Supramolecular Structure
of Self-Assembled Liposome/ε-Peptide/DNA Nanoparticles: Correlation
with Gene Delivery
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Abstract
Using solid-phase synthesis, lysine can be oligomerized
by a reaction
of the peptide carboxylate with the ε-amino group to produce
nontoxic, biodegradable cationic peptides, ε-oligo(l-lysines). Here α-substituted derivatives of such ε-oligo(l-lysines) containing arginine and histidine in the side chain
were tested as vectors for in vitro gene delivery. Combination of
ε-oligolysines with the cationic lipid DOTAP and plasmid DNA
resulted in transfection efficiency exceeding that of DOTAP alone,
without significant increase in cytotoxicity. Synchrotron small-angle
X-ray scattering studies revealed self-assembly of the DOTAP, ε-oligolysines,
and DNA to ordered lamellar complexes. High transfection efficiency
of the nanoparticles correlates with increase in zeta potential above
+20 mV and requires particle size to be below 500 nm. The synergistic
effect of branched ε-oligolysines and DOTAP in gene delivery
can be explained by the increase in surface charge and by the supramolecular
structure of the DOTAP/ε-oligolysine/DNA nanoparticles