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Bacteria-mediated delivery of nanoparticles and cargo into cells

Nature Nanotechnology volume 2, pages 441–449 (2007)Cite this article

Abstract

Nanoparticles and bacteria can be used, independently, to deliver genes and proteins into mammalian cells for monitoring or altering gene expression and protein production. Here, we show the simultaneous use of nanoparticles and bacteria to deliver DNA-based model drug molecules in vivo and in vitro. In our approach, cargo (in this case, a fluorescent or a bioluminescent gene) is loaded onto the nanoparticles, which are carried on the bacteria surface. When incubated with cells, the cargo-carrying bacteria (‘microbots’) were internalized by the cells, and the genes released from the nanoparticles were expressed in the cells. Mice injected with microbots also successfully expressed the genes as seen by the luminescence in different organs. This new approach may be used to deliver different types of cargo into live animals and a variety of cells in culture without the need for complicated genetic manipulations.

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Figure 1: Bacteria-mediated delivery of nanoparticles and cargo.
Figure 2: Internalization of microbots and their cargos.
Figure 3: Flow-cytometric assessment of microbot uptake by cells.
Figure 4: Intracellular delivery and expression of a model gene by microbots.
Figure 5: Microbot-mediated delivery and functional expression of luciferase gene in mice.
Figure 6: Characterization of in vivo protein expression.

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Acknowledgements

The authors would like to thank C. Koons, Drug Discovery Shared Resource of Purdue Cancer Center, for her help with the in vivo studies, S. Leavesly for his inputs in the initial bioluminescence imaging studies, C. Buck for assisting in the use of the facilities at Bindley Biosciences Center, and the Weldon School of Biomedical Engineering for funding the work. D.A. was supported by funds from NIH NIBIB.

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Authors and Affiliations

  1. Birck Nanotechnology Center, Purdue University, 1205 W State Street, West Lafayette, 47907, Indiana, USA

    Demir Akin & Rashid Bashir

  2. Bindley Biosciences Center, Purdue University, West Lafayette, 47907, Indiana, USA

    Demir Akin, Jennifer Sturgis, Kathy Ragheb, J. Paul. Robinson & Rashid Bashir

  3. Weldon School of Biomedical Engineering, Purdue University, 206 S Intramural Drive, West Lafayette, 47907, Indiana, USA

    Demir Akin, J. Paul. Robinson & Rashid Bashir

  4. Department of Basic Medical Sciences, Purdue University, West Lafayette, 47907, Indiana, USA

    Jennifer Sturgis, Kathy Ragheb & J. Paul. Robinson

  5. Department of Biology, Purdue University, West Lafayette, 47907, Indiana, USA

    Debby Sherman

  6. Department of Food Science, Molecular Food Microbiology Laboratory, 745 Agriculture Mall Drive, West Lafayette, 47907, Indiana, USA

    Kristin Burkholder & Arun K. Bhunia

  7. Department of Comparative Pathobiology, 725 Harrison Street, West Lafayette, 47907, Indiana, USA

    Sulma Mohammed

  8. School of Electrical and Computer Engineering, Purdue University, West Lafayette, 47907, Indiana, USA

    Rashid Bashir

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  1. Demir Akin
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Contributions

D.A. and R.B. designed the experiments. D.A. performed and was involved in all aspects of the experiments; J.S. performed confocal and fluorescence imaging; K.R. and J.P.R. performed the flow cytometery; and D.S. performed the SEM imaging. D.A., K.B. and A.B. designed and performed the cytotoxicity studies. S.M. assisted in in vivo studies. D.A. and R.B. co-wrote the paper.

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Correspondence to Demir Akin or Rashid Bashir.

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The authors declare no competing financial interests.

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Akin, D., Sturgis, J., Ragheb, K. et al. Bacteria-mediated delivery of nanoparticles and cargo into cells. Nature Nanotech 2, 441–449 (2007). https://doi.org/10.1038/nnano.2007.149

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