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.
Highlights
Recent years have seen a dramatic increase in interest regarding the use of gold nanoparticles (GNPs) as radiation sensitizers for radiotherapy [1]
Before investigations on the GNP distribution inside the cell and a quantification of the dose enhancement were made, the SmartFlare quenching concept was examined in order to verify a successful quenching of the release strand
cyanine 5 (Cy5) detection via epifluorescence microscopy (100x/ NA 1.44 objective, pixel size 64.5 nm) shows the release of the reporter strand, stating a successful SmartFlare binding around the cell nucleus
Summary
Recent years have seen a dramatic increase in interest regarding the use of gold nanoparticles (GNPs) as radiation sensitizers for radiotherapy [1]. This interest was initially driven by their high absorption of ionizing radiation and the resulting ability to increase the dose deposition within target volumes, even at low concentrations [2,3,4] leading to a significant RBE increase [3]. Dose enhancement effects of gold nanoparticles programme Open Access Publishing, by the Baden-Wurttemberg Ministry of Science, Research and the Arts and by Ruprecht-Karls-Universitat Heidelberg. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
