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금나노입자가 세포에 섭취되지 않았지만, 세포의 모양과 핵의 위치에 따라서 증가하는 선량과 해당 증가영역을 확인할 수 있습니다.

Abstract

The radiosensitization effect of gold nanoparticles (GNPs) has been demonstrated both in vitro and in vivo in radiation therapy. The purpose of this study was to systematically assess the biological effectiveness of GNPs distributed in the extracellular media for realistic cell geometries. TOPAS-nBio simulations were used to determine the nanometre-scale radial dose distributions around the GNPs, which were subsequently used to predict the radiation dose response of cells surrounded by GNPs. MDA-MB-231 human breast cancer cells and F-98 rat glioma cells were used as models to assess different cell geometries by changing (1) the cell shape, (2) the nucleus location within the cell, (3) the size of GNPs, and (4) the photon energy. The results show that the sensitivity enhancement ratio (SER) was increased up to a factor of 1.2 when the location of the nucleus is close to the cell membrane for elliptical-shaped cells. Heat-maps of damage-likelihoods show that most of the lethal events occur in the regions of the nuclei closest to the membrane, potentially causing highly clustered damage patterns. The effect of the GNP size on radiosensitization was limited when the GNPs were located outside the cell. The improved modelling of the cell geometry was shown to be crucial because the dose enhancement caused by GNPs falls off rapidly with distance from the GNPs. We conclude that radiosensitization can be achieved for kV photons even without cellular uptake of GNPs when the nucleus is shifted towards the cell membrane. Furthermore, damage was found to concentrate in a small region of the nucleus in close proximity to the extracellular, GNP-laden region. 

Author information

Sung W1, Ye SJ2, McNamara AL3, McMahon SJ4, Hainfeld J5, Shin J3, Smilowitz HM6, Paganetti H3, Schuemann J3.

1Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA. jschuemann@mgh.harvard.edu and Program in Biomedical Radiation Sciences, Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, South Korea. sye@snu.ac.kr and Biomedical Research Institute, Seoul National University College of Medicine, Seoul, South Korea.2Program in Biomedical Radiation Sciences, Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, South Korea. sye@snu.ac.kr and Biomedical Research Institute, Seoul National University College of Medicine, Seoul, South Korea and Robotics Research Laboratory for Extreme Environment, Advanced Institutes of Convergence Technology, Seoul National University, Suwon, South Korea.3Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA. jschuemann@mgh.harvard.edu and Harvard Medical School, Boston, Massachusetts, USA.4Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK.5Nanoprobes Inc. Yaphank, New York, USA.6UConn Health, Farmington, Connecticut, USA. 

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