title: 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.
authors.affiliation: 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.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, PR China.
authors.forename: Naimin
authors.initials: N
authors.lastname: Shao
authors.affiliation: Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, PR China.
authors.forename: Zhiqi
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, PR China.
authors.forename: Leqin
authors.initials: L
authors.lastname: Xu
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, PR China.
authors.forename: Changping
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, PR China; Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, PR China. Electronic address: yycheng@mail.ustc.edu.cn.
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, PR China. Electronic address: jianruxiao83@163.com.
authors.forename: Jianru
authors.initials: J
authors.lastname: Xiao
mesh_terms: D000818:Animals; D017209:Apoptosis; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry; D050091:Dendrimers / Q000737:chemistry*; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D010957:Plasmids / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics*; D014162:Transfection; D014227:Triazines / Q000737:chemistry*
chemical_list: D050091:Dendrimers; D008024:Ligands; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014227:Triazines; D004247:DNA
keywords: Dendrimer; Gene therapy; Osteosarcoma; TRAIL