Discover the SciOpen Platform and Achieve Your Research Goals with Ease.
Search articles, authors, keywords, DOl and etc.
Efficient DNA delivery is essential for introducing new genes into living cells. However, effective virus-based systems carry risks and efficient synthetic systems that are non-toxic remain to be discovered. The bottle-neck in synthetic systems is cytotoxicity, caused by the high concentration of DNA-condensing compounds required for efficient uptake of DNA. Here we report a polyethyleneimine (PEI) grafted ultra-small graphene oxide (PEI-g-USGO) for transfection. By removing the free PEI and ensuring a high PEI density on small sized graphene, we obtained very high transfection efficiencies combined with very low cytotoxicity. Plasmid DNA could be transfected into mammalian cell lines with up to 95% efficiency and 90% viability. Transfection in zebrafish embryos was 90%, with high viability, compared to efficiencies of 30% or lower for established transfection technologies. This result suggests a novel approach to the design of synthetic gene delivery vehicles for research and therapy.
Mastrobattista, E.; van der Aa, M. A. E. M.; Hennink, W. E.; Crommelin, D. J. A. Artificial viruses: A nanotechnological approach to gene delivery. Nat. Rev. Drug Discov. 2006, 5, 115-121.
Putnam, D. Polymers for gene delivery across length scales. Nat. Mater. 2006, 5, 439-451.
Kunath, K.; von Harpe, A.; Fischer, D.; Peterson, H.; Bickel, U.; Voigt, K.; Kissel, T. Low-molecular-weight polyethylenimine as a non-viral vector for DNA delivery: Comparison of physicochemical properties, transfection efficiency and in vivo distribution with high-molecular-weight polyethylenimine. J. Control. Release 2003, 89, 113-125.
Ogris, M.; Steinlein, P.; Kursa, M.; Mechtler, K.; Kircheis, R.; Wagner, E. The size of DNA/transferrin-PEI complexes is an important factor for gene expression in cultured cells. Gene Ther. 1998, 5, 1425-1433.
Lungwitz, U.; Breunig, M.; Blunk, T.; Göpferich, A. Polyethylenimine-based non-viral gene delivery systems. Eur. J. Pharm. Biopharm. 2005, 60, 247-266.
Godbey, W. T.; Wu, K. K.; Mikos, A. G. Size matters: Molecular weight affects the efficiency of poly(ethylenimine) as a gene delivery vehicle. J. Biomed. Mater. Res. 1999, 45, 268-275.
Behr, J. P. The proton sponge: A trick to enter cells the viruses did not exploit. Chimia 1997, 51, 34-36.
Sonawane, N. D.; Szoka, F. C.; Verkman, A. S. Chloride accumulation and swelling in endosomes enhances DNA transfer by polyamine-DNA polyplexes. J. Biol. Chem. 2003, 278, 44826-44831.
Clamme, J. P.; Azoulay, J.; Mely, Y. Monitoring of the formation and dissociation of polyethylenimine/DNA complexes by two photon fluorescence correlation spectroscopy. Biophys. J. 2003, 84, 1960-1968.
Boeckle, S.; von Gersdorff, K.; van der Piepen, S.; Culmsee, C.; Wagner, E.; Ogris, M. Purification of polyethylenimine polyplexes highlights the role of free polycations in gene transfer. J. Gene Med. 2004, 6, 1102-1111.
Boeckle, S.; Fahrmeir, J.; Roedl, W.; Ogris, M.; Wagner, E. Melittin analogs with high lytic activity at endosomal pH enhance transfection with purified targeted PEI polyplexes. J. Control. Release 2006, 112, 240-248.
Zintchenko, A.; Philipp, A.; Dehshahri, A.; Wagner, E. Simple modifications of branched PEI lead to highly efficient siRNA carriers with low toxicity. Bioconjugate Chem. 2008, 19, 1448-1455.
Zhang, L. M.; Lu, Z. X.; Zhao, Q. H.; Huang, J.; Shen, H.; Zhang, Z. J. Enhanced chemotherapy efficacy by sequential delivery of siRNA and anticancer drugs using PEI-grafted graphene oxide. Small 2011, 7, 460-464.
Yang, K.; Wan, J. M.; Zhang, S. A.; Zhang, Y. J.; Lee, S. T.; Liu, Z. A. In vivo pharmacokinetics, long-term biodistribution, and toxicology of PEGylated graphene in mice. ACS Nano 2011, 5, 516-522.
Chen, B. A.; Liu, M.; Zhang, L. M.; Huang, J.; Yao, J. L.; Zhang, Z. J. Polyethylenimine-functionalized graphene oxide as an efficient gene delivery vector. J. Mater. Chem. 2011, 21, 7736-7741.
Hummers, W. S.; Offeman, R. E. Preparation of graphitic oxide. J. Am. Chem. Soc. 1958, 80, 1339-1339.
Pan, D. Y.; Zhang, J. C.; Li, Z.; Wu, M. H. Hydrothermal route for cutting graphene sheets into blue-luminescent graphene quantum dots. Adv. Mater. 2010, 22, 734-738.
Robinson, J. T.; Tabakman, S. M.; Liang, Y. Y.; Wang, H. L.; Casalongue, H. S.; Vinh, D.; Dai, H. J. Ultrasmall reduced graphene oxide with high near-infrared absorbance for photothermal therapy. J. Am. Chem. Soc. 2011, 133, 6825-6831.
Moghimi, S. M.; Symonds, P.; Murray, J. C.; Hunter, A. C.; Debska, G.; Szewczyk, A. A two-stage poly(ethylenimine)-mediated cytotoxicity: Implications for gene transfer/therapy. Mol. Ther. 2005, 11, 990-995.
Gerlai, R. Zebrafish: An uncharted behavior genetic model. Behav. Genet. 2003, 33, 461-468.