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Simulation on the molecular radiosensitization effect of gold nanoparticles in cells irradiated by x-rays

 

Gold nanoparticles (GNPs) are high potential radiosensitizer agent in radiotherapy. Many studies have focused on the radiosensitization effect of GNPs in the cellular environment with x-ray irradiation. To better understand the physical foundation and to initially study the molecular radiosensitization effect within the nucleus, a cell model with a detailed DNA structure in the central nucleus was set up and complemented with different distributions of multiple GNPs in this work.


           In vitro investigations

With the Monte Carlo simulations, the radiosensitization effects on both physical quantities and primary biological responses, i.e. DNA strand breaks were simulated. The ratios of results under situations with GNPs compared to those without GNPs were defined as the enhancement factors (EFs). The simulation results show that the presence of GNPs can cause a notable enhancement effect on the energy deposition within a few micrometers from the border of GNPs. The greatest effect appears around the border and is mostly dominated by Auger electrons. Inside the nucleus, the enhancement effect on the DNA strand breakage becomes smaller because of the DNA distribution and the corresponding EFs are between 1 and 1.5. In the present simulation, multiple GNPs on the nucleus surface, the 60 kVp x-ray spectrum and the diameter of 100 nm are relatively more effective conditions for both physical and biological radiosensitization effects. These results indicate that GNP can be a good radiosensitizer in x-ray radiotherapy. The theoretical simulated results provide necessary information for the decision of using gold nanoparticle as a sensitizer agent in the preclinical and clinical radiotherapy. Based on this preliminary work, a joint cooperative project with the Department of Radiation Oncology at the Klinikum rechts der Isar, Technical University München on biological experiments with antibody-conjugated gold nanoparticles for treatment of breast cancer cells in mice has been granted by the Deutsche Forschungsgemeinschaft (DFG) for the next three years

 

 

              Preclinical application

Molecular model of cell and nucleus and distributions of GNPs in theoretical simulations

 

Enhancement factor of total DSB when a fixed number of GNPs are (a) indifferent distributions (various diameters, 60 kVp x-rays), and (b) around the nucleus surface (various diameters, various x-rays)

 

Importance for the Mission of Helmholtz Zentrum München:

Preclinical and clinical radiotherapy with x-rays could be benefit from the present theoretical study. Further joint biological experimental research project granted by the DFG with antibody-conjugated nanoparticles can promote the translational application of molecular targeted nanoparticles in the personalized radiotherapy in the near future.

Publication:

 Xie, W.Z.; Friedland, W.; Li, W.B.; Li, C.Y.; Oeh, U.; Qiu, R.; Li, J.L. and Hoeschen, C. Simulation on the molecular radiosensitization effect of gold nanoparticles in cells irradiated by x-rays (2015) Phys. Med. Biol. 60:6195–6212.