Efficient targeted gene delivery by a novel PAMAM/DNA dendriplex coated with hyaluronic acid

Aim: To design and develop a novel target-specific DNA-delivery system using hyaluronic acid (HA)–polyamidoamine (PAMAM) conjugates (P–HA). Materials & methods: The coupling of HA to the PAMAM dendrimer was analyzed by 1H-NMR and elemental analysis (CHN). Their properties were characterized in terms of size and zeta-potential and evaluated for in vitro and in vivo transfection efficiency. Results: The designed covalent HA-dendriplexes enhanced gene transfection of pCMV-Luc reporter gene in overexpressing CD44-receptor cancer cells. They were also more efficient in transfecting MDA-MB231 cells than conventional PEI-polyplexes. The cytotoxicity of the covalent HA-dendriplexes was lower than when using conventional polyethylenimine-polyplexes. In vivo studies showed that these targeted complexes were also efficient for delivering pCMVLuc in different organs of healthy mice, as well as in tumors of C57BL/6 animals. Conclusions: The HA-dendriplexes developed in this work may offer an advantageous alternative t...