Quantification and visualization of cellular uptake of TiO2 and Ag nanoparticles: Comparison of different ICP-MS techniques

I. Lun Hsiao, Frank S. Bierkandt, Philipp Reichardt, Andreas Luch, Yuh Jeen Huang, Norbert Jakubowski, Jutta Tentschert, Andrea Haase

Research output: Contribution to journalArticlepeer-review

81 Citations (Scopus)


Background: Safety assessment of nanoparticles (NPs) requires techniques that are suitable to quantify tissue and cellular uptake of NPs. The most commonly applied techniques for this purpose are based on inductively coupled plasma mass spectrometry (ICP-MS). Here we apply and compare three different ICP-MS methods to investigate the cellular uptake of TiO2 (diameter 7 or 20 nm, respectively) and Ag (diameter 50 or 75 nm, respectively) NPs into differentiated mouse neuroblastoma cells (Neuro-2a cells). Cells were incubated with different amounts of the NPs. Thereafter they were either directly analyzed by laser ablation ICP-MS (LA-ICP-MS) or were lysed and lysates were analyzed by ICP-MS and by single particle ICP-MS (SP-ICP-MS). Results: All techniques confirmed that smaller particles were taken up to a higher extent when values were converted in an NP number-based dose metric. In contrast to ICP-MS and LA-ICP-MS, this measure is already directly provided through SP-ICP-MS. Analysis of NP size distribution in cell lysates by SP-ICP-MS indicates the formation of NP agglomerates inside cells. LA-ICP-MS imaging shows that some of the 75 nm Ag NPs seemed to be adsorbed onto the cell membranes and were not penetrating into the cells, while most of the 50 nm Ag NPs were internalized. LA-ICPMS confirms high cell-to-cell variability for NP uptake. Conclusions: Based on our data we propose to combine different ICP-MS techniques in order to reliably determine the average NP mass and number concentrations, NP sizes and size distribution patterns as well as cell-to-cell variations in NP uptake and intracellular localization.

Original languageEnglish
Article number50
JournalJournal of Nanobiotechnology
Issue number1
Publication statusPublished - 2016
Externally publishedYes


  • Cellular internalization
  • Laser ablation ICP-MS
  • Nanoparticles
  • Neurons
  • Single particle ICP-MS

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Applied Microbiology and Biotechnology
  • Pharmaceutical Science


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