Various non-viral delivery systems for small interfering RNAs (
siRNA) have been developed. Such delivery systems generally exhibit tightly formed spherical structures. While such carriers have demonstrated good transfection activity in mono-layered cell systems, effects against solid
tumors are often less apparent and difficult to demonstrate, likely due to the rigid structures of the carriers, which may prevent penetration to deeper regions within
tumor tissue. Herein, we developed a flexible nanocarrier (FNC) system that is able to penetrate to deeper regions within
tumor tissue. Specifically, we employed previously found flexible polyplexes comprised of
siRNA and poly-
l-lysine as wick structures for the preparation of FNCs. FNCs were constructed by coating the wick structures with
lipids using a liposomal membrane fusion method. The diameters of the resulting FNCs were ca. 170nm, and the shapes were non-spherical.
Lipid coating was confirmed using a nuclease resistance assay. Furthermore, FNCs showed significant RNA interference effects, comparable to
Lipofectamine 2000, in a mono-layered cell system. To accelerate
tumor penetration, the FNC surface was modified with
polyethylene glycol (PEG) and the tight junction opener
peptide AT1002. Surface-modified FNCs demonstrated effective penetrability into a
cancer spheroid. Thus, we developed a novel and unique
tumor-penetrable
siRNA FNC system.