Quantifying the cellular uptake of semiconductor quantum dot nanoparticles by analytical electron microscopy

Nicole Hondow, M. Rowan Brown, Tobias Starborg, Alexander G. Monteith, Rik Brydson, Huw D. Summers, Paul Rees, Andy Brown

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Semiconductor quantum dot nanoparticles are in demand as optical biomarkers yet the cellular uptake process is not fully understood; quantification of numbers and the fate of internalized particles are still to be achieved. We have focussed on the characterization of cellular uptake of quantum dots using a combination of analytical electron microscopies because of the spatial resolution available to examine uptake at the nanoparticle level, using both imaging to locate particles and spectroscopy to confirm identity. In this study, commercially available quantum dots, CdSe/ZnS core/shell particles coated in peptides to target cellular uptake by endocytosis, have been investigated in terms of the agglomeration state in typical cell culture media, the traverse of particle agglomerates across U-2 OS cell membranes during endocytosis, the merging of endosomal vesicles during incubation of cells and in the correlation of imaging flow cytometry and transmission electron microscopy to measure the final nanoparticle dose internalized by the U-2 OS cells. We show that a combination of analytical transmission electron microscopy and serial block face scanning electron microscopy can provide a comprehensive description of the internalization of an initial exposure dose of nanoparticles by an endocytically active cell population and how the internalized, membrane bound nanoparticle load is processed by the cells. We present a stochastic model of an endosome merging process and show that this provides a data-driven modelling framework for the prediction of cellular uptake of engineered nanoparticles in general. Lay summary: Engineered nanoparticles offer potential for improved medical diagnosis and treatment. The particles are small enough to enter cells and we can monitor this process using electron microscopy. The microscopy provides the resolution to count numbers of nanoparticles internalized by cells so that we can know the exact dose received by a cell or cell population and the final fate of the nanoparticles.

Original languageEnglish (US)
Pages (from-to)167-176
Number of pages10
JournalJournal of Microscopy
Volume261
Issue number2
DOIs
StatePublished - Feb 1 2016

Keywords

  • Cellular uptake
  • Energy-filtered TEM
  • Nanoparticle dose
  • Quantum dots
  • SBF SEM
  • TEM

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

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