Fluorinated dendrimer for TRAIL gene therapy in cancer treatment

Abstract

The delivery of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene into cancer cells is a promising strategy for cancer treatment. However, the low transfection efficacy and/or the toxicity of vectors severely hamper the translation of TRAIL gene therapy into the clinics. In this article, we employed our recently developed fluorinated dendrimer as a vector to deliver plasmid encoding TRAIL (pTRAIL) into cancer cells for cancer treatment, which holds the advantages of both excellent transfection efficacy and low toxicity. Fluorinated poly(amidoamine) dendrimer (G4-F7₃₅) represented much higher TRAIL gene transfection efficacy than a series of transfection reagents including poly(ethylene imine) (PEI), SuperFect and Lipofectamine 2000, leading to a much higher cell apoptosis efficacy. The G4-F7₃₅/pTRAIL complex, compared with PEI/pTRAIL, could more efficiently destroy three-dimensional multicellular spheroids consisting of MDA-MB-231 cells, and suppress the tumor growth in vivo. Furthermore, G4-F7₃₅ showed minimal toxicity in vitro and undetectable systemic toxicity in vivo. From this study, the fluorinated dendrimer offers a promising prospect for TRAIL gene therapy.