Abstract
Non-viral gene-delivery systems are safer to use and easier to produce than viral vectors, but their comparatively low transfection efficiency has limited their applications1. Co-delivery of drugs and DNA has been proposed to enhance gene expression or to achieve the synergistic/combined effect of drug and gene therapies2,3,4,5,6. Attempts have been made to deliver drugs and DNA simultaneously using liposomes7. Here we report cationic core–shell nanoparticles that were self-assembled from a biodegradable amphiphilic copolymer. These nanoparticles offer advantages over liposomes, as they are easier to fabricate, and are more readily subject to modulation of their size and degree of positive charge. More importantly, they achieve high gene-transfection efficiency and the possibility of co-delivering drugs and genes to the same cells. Enhanced gene transfection with the co-delivery of paclitaxel has been demonstrated by in vitro and in vivo studies. In particular, the co-delivery of paclitaxel with an interleukin-12-encoded plasmid using these nanoparticles suppressed cancer growth more efficiently than the delivery of either paclitaxel or the plasmid in a 4T1 mouse breast cancer model. Moreover, the co-delivery of paclitaxel with Bcl-2-targeted small interfering RNA (siRNA) increased cytotoxicity in MDA-MB-231 human breast cancer cells.
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Acknowledgements
The authors thank K. W. Leong (Johns Hopkins School of Medicine), J. Y. Ying (Institute of Bioengineering and Nanotechnology (IBN)), S. Wang (IBN), X.-G. Wang (Tsinghua University, P. R. China) and S. H. Goh (National University of Singapore) for valuable discussions. They acknowledge the technical assistance and contribution of X. Jiang (Johns Hopkins Singapore), C.-W. Tan, R. Ruan and K.-H. Foong (IBN). This work was funded by the IBN (Agency for Science, Technology and Research, Singapore).
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Y.W. was responsible for polymer synthesis and in vitro experiments, and worked on animal experiments together with S.G. W.-H.Y. and H.S.Y. were responsible for siRNA experiments. Y.-Y.Y. was in charge of polymer design, project initiation, project planning and overseeing the project.
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Wang, Y., Gao, S., Ye, WH. et al. Co-delivery of drugs and DNA from cationic core–shell nanoparticles self-assembled from a biodegradable copolymer. Nature Mater 5, 791–796 (2006). https://doi.org/10.1038/nmat1737
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DOI: https://doi.org/10.1038/nmat1737
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