Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, PR China; Department of Spine Surgery, First Affiliated Hospital of Wenzhou Medical University, Zhejiang 325000, PR China.
Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, PR China.
Acta Biomater. 2015 Apr;17:115-24. doi: 10.1016/j.actbio.2015.01.007. Epub 2015 Jan 14.
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.
骨肉瘤是一种高级别的恶性骨肿瘤，通常发生在青少年中。尽管治疗有所改善，但对于治疗无反应或转移的患者，五年生存率仍然很差。肿瘤坏死因子（TNF）相关凋亡诱导配体（TRAIL）基因治疗是癌症治疗的一种新策略，然而，缺乏高效低毒的载体仍然是 TRAIL 基因治疗的主要障碍。在这项研究中，合成了一种三嗪修饰的树枝状大分子 G5-DAT66，并将其用作 TRAIL 基因治疗的载体，进行了体内和体外研究。与脂质体 2000和 SuperFect 等商业转染试剂相比，该材料对骨肉瘤 MG-63 细胞系的转染效率更高。当递送 TRAIL 质粒时，它能有效地诱导 MG-63 细胞和三维 MG-63 细胞培养物发生凋亡。体内研究进一步证明，G5-DAT66 能有效地将 TRAIL 质粒转染入肿瘤，并抑制骨肉瘤荷瘤小鼠的肿瘤生长。这些结果表明，三嗪修饰的树枝状大分子在骨肉瘤的 TRAIL 基因治疗中具有广阔的应用前景。
