Abstract Gene therapies represent a promising
therapeutic route for liver cancers, but major challenges remain in the
design of safe and efficient gene-targeting delivery systems. For
example, cationic polymers show good transfection efficiency as gene
carriers, but are hindered by cytotoxicity and non-specific targeting.
Here we report a versatile method of one-step conjugation of
glycyrrhetinic acid (GA) to reduce cytotoxicity and improve the
cultured liver cell -targeting capability of cationic polymers. We have
explored a series of cationic polymer derivatives by coupling different
ratios of GA to polypropylenimine (PPI) dendrimer. These new gene
carriers (GA-PPI dendrimer) were systematically characterized by
UV-vis,1H NMR titration, electron microscopy, zeta potential, dynamic
lightscattering, gel electrophoresis, confocal microscopy and flow
cytometry. We demonstrate that GA-PPI dendrimers can efficiently load
and protect pDNA, via formation of nanostructured GA-PPI/pDNA
polyplexes. With optimal GA substitution degree (6.31%), GA-PPI
dendrimers deliver higher liver cell transfection efficiency (43.5% vs
22.3%) and lower cytotoxicity (94.3% vs 62.5%, cell viability) than the
commercial bench-mark DNA carrier bPEI (25kDa) with cultured liver
model cells (HepG2). There results suggest that our new GA-PPI
dendrimer are a promising candidate gene carrier for targeted liver
cancer therapy. One-step.pdf
|