Dose enhancement effects of gold nanoparticles specifically targeting RNA in breast cancer cells

Georg Hildenbrand; Philipp Metzler; Götz Pilarczyk; Vladimir Bobu; Wilhelm Kriz; Hiltraud Hosser; Jens Fleckenstein; Matthias Krufczik; Felix Bestvater; Frederik Wenz; Michael Hausmann

doi:10.1371/journal.pone.0190183

Dose enhancement effects of gold nanoparticles specifically targeting RNA in breast cancer cells

PLoS One. 2018 Jan 18;13(1):e0190183. doi: 10.1371/journal.pone.0190183. eCollection 2018.

Authors

Affiliations

¹ Kirchhoff-Institute for Physics, Faculty of Physics and Astronomy, Heidelberg University, Heidelberg, Germany.
² Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim at Heidelberg University, Mannheim, Germany.
³ Department of Neuroanatomy, Center for Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty Mannheim at Heidelberg University, Mannheim, Germany.
⁴ Light Microscopy Faculty, German Cancer Research Centre (DKFZ), Heidelberg, Germany.

Abstract

Localization microscopy has shown to be capable of systematic investigations on the arrangement and counting of cellular uptake of gold nanoparticles (GNP) with nanometer resolution. In this article, we show that the application of specially modified RNA targeting gold nanoparticles ("SmartFlares") can result in ring like shaped GNP arrangements around the cell nucleus. Transmission electron microscopy revealed GNP accumulation in vicinity to the intracellular membrane structures including them of the endoplasmatic reticulum. A quantification of the radio therapeutic dose enhancement as a proof of principle was conducted with γH2AX foci analysis: The application of both-SmartFlares and unmodified GNPs-lead to a significant dose enhancement with a factor of up to 1.2 times the dose deposition compared to non-treated breast cancer cells. This enhancement effect was even more pronounced for SmartFlares. Furthermore, it was shown that a magnetic field of 1 Tesla simultaneously applied during irradiation has no detectable influence on neither the structure nor the dose enhancement dealt by gold nanoparticles.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Breast Neoplasms / genetics
Breast Neoplasms / pathology*
Cell Line, Tumor
Gold / chemistry*
Humans
Metal Nanoparticles* / chemistry
RNA, Neoplasm / drug effects*

Substances

RNA, Neoplasm
Gold

Grants and funding

The support of the Innovation Fund “Frontier” of the Heidelberg University within the excellence initiative of the Deutsche Forschungsgemeinschaft (DFG) to Georg Hildenbrand and Michael Hausmann is gratefully acknowledged. In addition, we acknowledge financial support by Deutsche Forschungsgemeinschaft within the funding programme Open Access Publishing, by the Baden-Württemberg Ministry of Science, Research and the Arts and by Ruprecht-Karls-Universität Heidelberg. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.