Triazine-modified dendrimer for efficient TRAIL gene therapy in osteosarcoma.

Abstract

Osteosarcoma is a high-grade malignant bone tumor that usually develops in the teenagers. Despite improvement in therapy, the five-year survival rate is poor for patients not responding to treatment or with metastases. Tumor necrosis factor (TNF) related apoptosis inducing ligand (TRAIL) gene therapy is a new strategy in the treatment of cancers, however, the lack of efficient and low toxic vectors remains the major obstacle in TRAIL gene therapy. In this study, a triazine-modified dendrimer G5-DAT66 was synthesized and used as a vector for TRAIL gene therapy in vitro and in vivo. The material shows much higher transfection efficacy on osteosarcoma MG-63 cell line than commercial transfection reagents such as Lipofectamine 2000 and SuperFect. It effectively induces apoptosis in MG-63 cells and three-dimensional MG-63 cell cultures when delivering a TRAIL plasmid. In vivo studies further prove that G5-DAT66 efficiently transfects TRAIL plasmid in tumors and inhibits tumor growth in osteosarcoma-bearing mice. These results suggest that triazine-modified dendrimer has promising potential for TRAIL gene therapy in osteosarcoma.