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Enhanced motility of alveolar cancer cells induced by CpG-ODN-functionalized nanoparticles

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Abstract

Lysosomal TLR-9 is stimulated in A549 lung epithelial cells through administration of nanoparticles (NPs) either based on γ-Fe2O3 or MnO. Synthetic single-stranded immunostimulatory CpG-oligodeoxynucleotides (CpG-ODN) are covalently attached to fluorescently labelled γ-Fe2O3- and MnO-NPs in order to monitor the impact of TLR-9 activation on motility and cell morphology employing time-resolved impedance spectroscopy. In contrast to cytotoxic MnO-based particles, particles made from Fe2O3 are non-toxic carriers for pathogen-mimicking CpG-ODNs, which efficiently stimulate endogenous TLR-9, resulting in enhanced micromotility and a loss of barrier properties. Compared to neat CpG-ODNs administered in the absence of particles, the nucleotides displayed by NPs are found to be considerably more efficient in stimulating A549 cells attributed to a larger local concentration of ligands on the particles’ surface. The study shows that particle-based CpG-ODNs added to tumour cells increase their motility even further and therefore might also enhance their invasiveness and metastatic potential, foiling the original strategy of immunotherapy.

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Acknowledgements

We thank Dr. Patrick Theato and Florian D. Jochum for preparation of the polymer for coating the particles. We thank Anja Herdlitschke and Angela Rübeling for cell preparation. Financial support was provided by SPP1313 ‘Bionanoresponse’, Boehringer Ingelheim Fonds (J.R., University of Goettingen), Dorothea Schloezer fellowship (A.P., University of Goettingen), POLYMAT (K.K., University of Mainz) and the Carl-Zeiss Foundation (T.D.S.). I.S. acknowledges a ‘Fonds der Chemischen Industrie VCI’ Fellowship and is a recipient of a fellowship through the Excellence Initiative (DFG/GSC 266).

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Authors and Affiliations

  1. Institute of Physical Chemistry, Tammannstr. 6, 37077, Goettingen, Germany

    Jan Rother, Anna Pietuch & Andreas Janshoff

  2. Institute of Inorganic and Analytical Chemistry, Duesbergweg 10-14, 55122, Mainz, Germany

    Kerstin Koll, Thomas D. Schladt, Oskar Köhler, Isabel Schick & Wolfgang Tremel

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  1. Jan Rother
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  2. Anna Pietuch
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  3. Kerstin Koll
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  4. Thomas D. Schladt
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  5. Oskar Köhler
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  6. Isabel Schick
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  7. Wolfgang Tremel
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  8. Andreas Janshoff
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Correspondence to Andreas Janshoff.

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Rother, J., Pietuch, A., Koll, K. et al. Enhanced motility of alveolar cancer cells induced by CpG-ODN-functionalized nanoparticles. J Nanopart Res 15, 2107 (2013). https://doi.org/10.1007/s11051-013-2107-2

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  • DOI: https://doi.org/10.1007/s11051-013-2107-2

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