Modified PAMAM vehicles for effective TRAIL gene delivery to colon adenocarcinoma: in vitro and in vivo evaluation.

TRAIL (tumour necrosis factor-related apoptosis-inducing ligand) gene therapy is considered as one of the promising approaches for cancer treatment. Polyamidoamine (PAMAM) is one of the most extensively applied polymeric vector in gene delivery. In the current study, PAMAM (G4 and G5) dendrimers were modified with alkyl-carboxylate chain, PEG and cholesteryl chloroformate in order to enhance transfection efficiency through overcoming extracellular and intracellular barriers while reducing PAMAM cytotoxicity. Gene delivery efficiency of synthetized vectors was evaluated by both GFP (green fluorescent protein) reporter gene and TRAIL plasmid in colon cancer cells, in vitro and in vivo. The obtained results demonstrated that PAMAM G4-alkyl-PEG (3%)-Chol (5%)-TRAIL complexes at C/P ratio 4 could significantly increase cell death (29.45%) in comparison with unmodified PAMAM vector (15.5%). Moreover, in vivo study in C26 tumor-bearing BALB/c mice suggested that the prepared non-toxic safe vector could inhibit the tumor growth. This study represented the potent vehicle based on cholesterol-grafted PAMAM dendrimers with alkyl-PEG modification for efficient gene delivery in vitro and in vivo.