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The use of folate-PEG-grafted-hybranched-PEI nonviral vector for the inhibition of glioma growth in the rat
Authors:Bing Liang  Ming-Liang He  Chu-yan Chan  Yang-chao Chen  Xiang-Ping Li  Yi Li  Dexian Zheng  Marie C Lin  Hsiang-Fu Kung  Xin-Tao Shuai  Ying Peng
Institution:1. Department of Neurology, The Second Affiliated Hospital, Sun Yat-sen University, No. 107 West Road of Riverside, Guangzhou 510120, China;2. Biomedical Engineering Center, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China;3. The Center for Emerging Infectious, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong;4. Department of Otolaryngology, Nanfang Hospital, Nanfang Medical University, Guangzhou, China;5. Department of Chemistry, The University of Hong Kong, Hong Kong;6. Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, China;1. Molecular Neurotherapy and Imaging Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA;2. Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA;3. Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA;4. Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA;1. School of Veterinary Medicine, Liaoning Medical University, Jinzhou 121000, PR China;2. Central Laboratory of Liaoning Medical University, Jinzhou 121000, PR China;3. School of Pharmacy, Liaoning Medical University, Jinzhou 121000, PR China;1. Center for Pharmaceutical Biotechnology & Nanomedicine, Northeastern University, Boston, MA 02115, United States;2. Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M University Health Science Center, Kingsville, TX 78363, United States;1. Department of Agricultural Biotechnology & Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, South Korea;2. Institute of Green-Bio Science & Technology, Seoul National University, Pyeongchanggun, Gangwondo 232-916, South Korea
Abstract:Combined treatment using nonviral agent-mediated enzyme/prodrug therapy and immunotherapy had been proposed as a powerful alternative method of cancer therapy. The present study was aimed to evaluate the cytotoxicity in vitro and the therapeutic efficacy in vivo when the cytosine deaminase/5-fluorocytosine (CD/5-FC) and TNF-related apoptosis-inducing ligand (TRAIL) genes were jointly used against rat C6 glioma cells. The potency of the FA-PEG-PEI used as a nonviral vector was tested in the FR-expressed C6 glioma cells and Wistar rats. The C6 glioma cells and animal model were treated by the combined application of FA-PEG-PEI/pCD/5-FC and FA-PEG-PEI/pTRAIL. The antitumor effect was evaluated by survival assays and tumor volume. This study revealed a significant increase of cytotoxicity in vitro following the combined application of FA-PEG-PEI/pCD/5-FC and FA-PEG-PEI/pTRAIL treatments in C6 glioma cells. Animal studies showed a significant growth inhibition of the C6 glioma xenografts using the combined treatment. These results demonstrated that the combined treatment generated additive cytotoxic effect in C6 glioma cells in both in vitro and in vivo conditions, and indicated that such treatment method using both enzyme/prodrug therapy and TRAIL immunotherapy might be a promising therapeutic strategy in treating glioma.
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