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Statistical analysis of nanoparticle dosing in a dynamic cellular system

Nature Nanotechnology volume 6, pages 170–174 (2011)Cite this article

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Abstract

The delivery of nanoparticles into cells is important in therapeutic applications1,2,3 and in nanotoxicology4. Nanoparticles are generally targeted to receptors on the surfaces of cells and internalized into endosomes by endocytosis5,6,7,8,9, but the kinetics of the process and the way in which cell division redistributes the particles remain unclear. Here we show that the chance of success or failure of nanoparticle uptake and inheritance is random. Statistical analysis of nanoparticle-loaded endosomes indicates that particle capture is described by an over-dispersed Poisson probability distribution that is consistent with heterogeneous adsorption and internalization. Partitioning of nanoparticles in cell division is random and asymmetric, following a binomial distribution with mean probability of 0.52–0.72. These results show that cellular targeting of nanoparticles is inherently imprecise due to the randomness of nature at the molecular scale, and the statistical framework offers a way to predict nanoparticle dosage for therapy and for the study of nanotoxins.

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Figure 1: Schematic of nanoparticle delivery and loading into cells.
Figure 2: Optical tracking using photonic nanoparticles.
Figure 3: Nanoparticle delivery to cells.
Figure 4: Nanoparticle dose inheritance.

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Acknowledgements

The authors thank N. Hondow and A. Brown for the electron micrograph of quantum dots and P. Williams for the DLS data. This work was supported by the Engineering and Physical Sciences Research Council, UK (grant no. EP/H008683/1, ‘Nanoparticle Cytometrics’) and the European Regional Development Funded Swansea Centre for Nanohealth.

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Authors and Affiliations

  1. Centre for Nanohealth, College of Engineering, Swansea University, Swansea, SA2 8PP, UK

    Huw D. Summers, Paul Rees, Mark D. Holton & M. Rowan Brown

  2. School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK

    Sally C. Chappell, Paul J. Smith & Rachel J. Errington

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  1. Huw D. Summers
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Contributions

H.D.S., P.R., R.J.E. and P.J.S. designed the experiments. H.D.S., P.R. and M.R.B. analysed the data. H.D.S. and P.R. wrote the manuscript in close collaboration with the other authors. M.D.H and S.C. performed cell culture and nanoparticle loading. M.D.H. performed flow cytometry measurements. All authors discussed the results and approved the final version of the manuscript.

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Correspondence to Huw D. Summers.

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The authors declare no competing financial interests.

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Summers, H., Rees, P., Holton, M. et al. Statistical analysis of nanoparticle dosing in a dynamic cellular system. Nature Nanotech 6, 170–174 (2011). https://doi.org/10.1038/nnano.2010.277

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