Quantification of nanoparticle dose and vesicular inheritance in proliferating cells

Huw D. Summers, Martyn R. Brown, Mark D. Holton, James A. Tonkin, Nicole Hondow, Andrew P. Brown, Rik Brydson, Paul Rees

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Assessing dose in nanoparticle-cell interactions is inherently difficult due to a complex multiplicity of possible mechanisms and metrics controlling particle uptake. The fundamental unit of nanoparticle dose is the number of particles internalized per cell; we show that this can be obtained for large cell populations that internalize fluorescent nanoparticles by endocytosis, through calibration of cytometry measurements to transmission electron microscopy data. Low-throughput, high-resolution electron imaging of quantum dots in U-2 OS cells is quantified and correlated with high-throughput, low-resolution optical imaging of the nanoparticle-loaded cells. From the correlated data, we obtain probability distribution functions of vesicles per cell and nanoparticles per vesicle. Sampling of these distributions and comparison to fluorescence intensity histograms from flow cytometry provide the calibration factor required to transform the cytometry metric to total particle dose per cell, the mean value of which is 2.4 million. Use of the probability distribution functions to analyze particle partitioning during cell division indicates that, while vesicle inheritance is near symmetric, highly variable vesicle loading leads to a highly asymmetric particle dose within the daughter cells.

Original languageEnglish (US)
Pages (from-to)6129-6137
Number of pages9
JournalACS Nano
Volume7
Issue number7
DOIs
StatePublished - Jul 23 2013

Keywords

  • electron microscopy
  • flow cytometry
  • nanoparticle dose
  • nanoparticle inheritance

ASJC Scopus subject areas

  • Engineering(all)
  • Materials Science(all)
  • Physics and Astronomy(all)

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