Hildenbrand Georg, Metzler Philipp, Pilarczyk Götz, Bobu Vladimir, Kriz Wilhelm, Hosser Hiltraud, Fleckenstein Jens, Krufczik Matthias, Bestvater Felix, Wenz Frederik, Hausmann Michael
Kirchhoff-Institute for Physics, Faculty of Physics and Astronomy, Heidelberg University, Heidelberg, Germany.
Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim at Heidelberg University, Mannheim, Germany.
PLoS One. 2018 Jan 18;13(1):e0190183. doi: 10.1371/journal.pone.0190183. eCollection 2018.
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.
定位显微镜已被证明能够以纳米分辨率对金纳米颗粒(GNP)的细胞摄取排列和计数进行系统研究。在本文中,我们表明,应用经过特殊修饰的靶向RNA的金纳米颗粒(“智能荧光”)可导致细胞核周围出现环状GNP排列。透射电子显微镜显示GNP在内质网等细胞内膜结构附近积累。通过γH2AX焦点分析对放射治疗剂量增强作为原理证明进行了定量:与未处理的乳腺癌细胞相比,应用“智能荧光”和未修饰的GNP均导致剂量显著增强,增强因子高达剂量沉积的1.2倍。这种增强效应在“智能荧光”中更为明显。此外,研究表明,在辐照期间同时施加1特斯拉的磁场对金纳米颗粒的结构和剂量增强均无可检测到的影响。