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Relating surface-enhanced Raman scattering signals of cells to gold nanoparticle aggregation as determined by LA-ICP-MS micromapping

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Abstract

The cellular response to nanoparticle exposure is essential in various contexts, especially in nanotoxicity and nanomedicine. Here, 14-nm gold nanoparticles in 3T3 fibroblast cells are investigated in a series of pulse-chase experiments with a 30-min incubation pulse and chase times ranging from 15 min to 48 h. The gold nanoparticles and their aggregates are quantified inside the cellular ultrastructure by laser ablation inductively coupled plasma mass spectrometry micromapping and evaluated regarding the surface-enhanced Raman scattering (SERS) signals. In this way, both information about their localization at the micrometre scale and their molecular nanoenvironment, respectively, is obtained and can be related. Thus, the nanoparticle pathway from endocytotic uptake, intracellular processing, to cell division can be followed. It is shown that the ability of the intracellular nanoparticles and their accumulations and aggregates to support high SERS signals is neither directly related to nanoparticle amount nor to high local nanoparticle densities. The SERS data indicate that aggregate geometry and interparticle distances in the cell must change in the course of endosomal maturation and play a critical role for a specific gold nanoparticle type in order to act as efficient SERS nanoprobe. This finding is supported by TEM images, showing only a minor portion of aggregates that present small interparticle spacing. The SERS spectra obtained after different chase times show a changing composition and/or structure of the biomolecule corona of the gold nanoparticles as a consequence of endosomal processing.

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Acknowledgements

We thank S. Selve (ZELMI TU Berlin) for TEM support, R. Schneider (BAM Federal Institute for Materials Research and Testing) for providing access to the cell culture facility, A. Cossmer (BAM) for ICP-MS analysis and P. Lasch (CytoSpec, Inc.) for Cytospec software. Financial support from ERC grant no. 259432 (T.B, D.D., J.K.) is gratefully acknowledged.

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Correspondence to Janina Kneipp.

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Published in the topical collection Single Cell Analysis with guest editors Petra Dittrich and Norbert Jakubowski.

T. Büchner and D. Drescher contributed equally to this work.

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Büchner, T., Drescher, D., Traub, H. et al. Relating surface-enhanced Raman scattering signals of cells to gold nanoparticle aggregation as determined by LA-ICP-MS micromapping. Anal Bioanal Chem 406, 7003–7014 (2014). https://doi.org/10.1007/s00216-014-8069-0

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  • DOI: https://doi.org/10.1007/s00216-014-8069-0

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