Abstract
Successfully systemic gene therapy has been hindered by vector-related limitations, including toxicity and inefficient gene delivery to tumor cells after intravenous administration. In this study, we evaluated the potential of spherical polyethylenimine nanogels (M-PEIs) as a novel vector for intravenous delivery of plasmids to tumor cells. M-PEIs provided a sustained release of plasmids up to 14 days and were also effective in protecting plasmids from enzymatic degradation in serum-conditioned media. M-PEIs showed no obvious cytotoxicity to mammalian cells in vitro as well as to liver, heart and kidney in mice after intravenous injection. Importantly, following intravenous administration of M-PEIs/plasmid complexes into human hepatocellular carcinoma xenograft-bearing mice, green fluorescence protein reporter gene expression was predominantly found in the tumor. This study indicates that M-PEIs may be a candidate for systemic delivery of plasmids into tumors.
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Acknowledgements
This work is supported by grants from National Natural Science Foundation of China, Ministry of Science and Technology of China (973 and 863 project), Shanghai Commission of Science and Technology, a special grant from E-Institute of Shanghai University's Immunology Division and National Foundation for Excellence Doctoral Project and Shanghai Municipal Education Commission for Shuguang Project.
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Dong, L., Xu, H., Liu, YB. et al. M-PEIs nanogels: potential nonviral vector for systemic plasmid delivery to tumor cells. Cancer Gene Ther 16, 561–566 (2009). https://doi.org/10.1038/cgt.2009.11
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DOI: https://doi.org/10.1038/cgt.2009.11
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