Poly(ethylene glycol) analogs grafted with low molecular weight poly(ethylene imine) as non-viral gene vectors |
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| Authors: | Zhenfang Zhang Cuihong Yang Yajun Duan Yanming Wang Jianfeng Liu Lianyong Wang Deling Kong |
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| Institution: | 1. The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University, Tianjin 300071, PR China;2. Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin 300192, PR China;1. Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, USA;2. Department of Statistics, Brigham Young University, Provo, UT 84602, USA;1. Department of Pharmacy, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tenpaku, Nagoya 468-8503, Japan;2. Department of Pharmacy, Faculty of Pharmacy, Aomori University, 2-3-1 Kobata, Aomori 030-0943, Japan;3. Department of Life Sciences, Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, 562 Nanatsuka, Shobara 727-0023, Japan;4. Laboratory of Food Chemistry, Department of Life Sciences, Junior College, Gifu Shotoku Gakuen University, 1-38 Nakauzura, Gifu 055-8288, Japan;5. Department of Health Promotion Sciences, Graduate School of Human Health Sciences, Tokyo Metropolitan University, 1-1 Minamiosawa, Hachioji 192-0397, Japan;1. State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Functional Polymer Materials, Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, PR China;2. Department of Biomedical Engineering, University of Groningen and University Medical Center Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands;3. Department of Orthodontics, University of Groningen and University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands;4. Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, PR China;1. Department of Polymer Science and Technology and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China;2. Tianjin Key Laboratory of Radiation Molecular and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin 300192, China;3. Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China;1. Key Laboratory of Bioactive Materials, Ministry of Education, State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Collaborative Innovation Center of Chemical Science and Engineering, and National Institute of Functional Materials, Nankai University, Tianjin 300071, PR China;2. Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, PR China;3. Henan Key Laboratory of Immunology and Targeted Drug, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan 453003, PR China;4. Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221004, PR China;1. Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China;2. College of Chemistry & Pharmacy, Shaanxi Key Laboratory of Natural Products & Chemical Biology, Northwest A&F University, Shaanxi 712100, China |
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| Abstract: | A novel class of non-viral gene vectors consisting of low molecular weight poly(ethylene imine) (PEI) (molecular weight 800 Da) grafted onto degradable linear poly(ethylene glycol) (PEG) analogs was synthesized. First, a Michael addition reaction between poly(ethylene glycol) diacrylates (PEGDA) (molecular weight 258 Da) and d,l-dithiothreitol (DTT) was carried out to generate a linear polymer (PEG–DTT) having a terminal thiol, methacrylate and pendant hydroxyl functional groups. Five PEG–DTT analogs were synthesized by varying the molar ratio of diacrylates to thiols from 1.2:1 to 1:1.2. Then PEI (800 Da) was grafted onto the main chain of the PEG–DTTs using 1,1′-carbonyldiimidazole as the linker. The above reaction gave rise to a new class of non-viral gene vectors, (PEG–DTT)–g-PEI copolymers, which can effectively complex DNA to form nanoparticles. The molecular weights and structures of the copolymers were characterized by gel permeation chromatography, 1H nuclear magnetic resonance and Fourier transform infrared spectroscopy. The size of the nanoparticles was <200 nm and the surface charge of the nanoparticles, expressed as the zeta potential, was between +20 and +40 mV. Cytotoxicity assays showed that the copolymers exhibited much lower cytotoxicities than high molecular weight PEI (25 kDa). Transfection was performed in cultured HeLa, HepG2, MCF-7 and COS-7 cells. The copolymers showed higher transfection efficiencies than PEI (25 kDa) tested in four cell lines. The presence of serum (up to 30%) had no inhibitory effect on the transfection efficiency. These results indicate that this new class of non-viral gene vectors may be a promising gene carrier that is worth further investigation. |
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