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.