Development of targeted gene delivery system based on liposome and PAMAM dendrimer functionalized with hyaluronic acid and TAT peptide: In vitro and in vivo studies.

Abstract

The development of gene delivery systems is essential to improve their transfection efficiency and cytotoxicity. Combination of lipid and polymeric nanoparticles with the characteristics of both systems have been considered as a next-generation gene delivery platform. In the current study, we designed a novel and efficient targeted gene delivery system based on liposome and PAMAM dendrimer in cancer cells. Two polymeric formulations containing polyamidoamine-TAT (PAMAM-TAT) and PAMAM-TAT-Hyaluronic acid (HA) and two lipopolymeric carriers including PAMAM-TAT-Liposome and PAMAM-TAT-HA-Liposome were complexed with the enhanced green fluorescent protein (EGFP) plasmid and then evaluated in terms of physicochemical characteristics. The cytotoxicity and transfection efficiency of these synthetized carriers were accomplished against murine colon carcinoma cell line (C26). The biodistribution of polyplexes and lipoployplexes was also evaluated in the C26 tumor bearing mice. The results showed no significant toxicity for all designed nanoparticles (NPs) in C/P4. The highest gene expression was observed using lipopolyplex PAMAM-TAT-HA-Liposome in C/P4 (ratio polymer/DNA; wt/wt). Biodistribution study demonstrated more aggregation of targeted lipopolyplex in tumor cells than other nanoparticles (NPs). It could be concluded that the developed targeted lipopolymeric complex could serve as promising nanotherapeutic system for gene therapy.