Abstract
Dose enhancement by gold nanoparticles (AuNP) increases the biological effectiveness of radiation damage in biomolecules and tissue. To apply them effectively during cancer therapy their influence on the locally delivered dose has to be determined. Hereby, the AuNP locations strongly influence the energy deposit in the nucleus, mitochondria, membrane and the cytosol of the targeted cells. To estimate these effects, particle scattering simulations are applied. In general, different approaches for modeling the AuNP and their distribution within the cell are possible. In this work, two newly developed continuous and discrete-geometric models for simulations of AuNP in cells are presented. These models are applicable to simulations of internal emitters and external radiation sources. Most of the current studies on AuNP focus on external beam therapy. In contrast, we apply the presented models in Monte-Carlo particle scattering simulations to characterize the energy deposit in cell organelles by radioactive 198AuNP. They emit beta and gamma rays and are therefore considered for applications with solid tumors. Differences in local dose enhancement between randomly distributed and nucleus targeted nanoparticles are compared. Hereby nucleus targeted nanoparticels showed a strong local dose enhancement in the radio sensitive nucleus. These results are the foundation for future experimental work which aims to obtain a mechanistic understanding of cell death induced by radioactive 198Au.
Highlights
In this work we have presented combine cell-nanoparticle models for Topas/Geant[4] to simulate the local dose enhancement effects caused by the presence of nanoparticles in the cytoplasm, as well as on the nucleus surface of cells
The models were applied to determine the energy deposit caused by the presence of radioactive AuNP nanoparticles in CHO cells
Simulations were performed for continuous and a discrete-geometric AuNP models. These discrete-geometric nanoparticle models enable the simulation of non-homogeneous distribution of AuNP within the cell
Summary
Particle scattering simulations.To obtain the energy deposit in different cell organelles Monte Carlo simulations (MCS) based on the Geant[4] MCS framework (10.06)[29,30,31] in combination with the Topas (3.5)[32] interface and the Topas-nBio[28] extensions were performed. During the simulations the position of the radioactive decay was chosen randomly within the active material It has to be taken into account, that the scattering-models applied in the AuNP region have a recommended low energy limit of 100 eV. Simulations should preferentially be performed with track-structure code which enables step-by-step simulations of the scattering interactions, and results in a higher accuracy compared to condensed-history code[50,54] This situation will improve in the future when the newly implemented scattering models for gold as implemented by Sakata et al become available in future releases of Geant[4] and T opas[48,49,50].
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