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用于研究细胞器中辐射剂量增强的 TOPAS 联合细胞和纳米颗粒模型。

Combined cell and nanoparticle models for TOPAS to study radiation dose enhancement in cell organelles.

机构信息

Bundesanstalt für Materialforschung und -prüfung, 12205, Berlin, Germany.

Institut für Experimentalphysik, Freie Universität Berlin, 14195, Berlin, Germany.

出版信息

Sci Rep. 2021 Mar 24;11(1):6721. doi: 10.1038/s41598-021-85964-2.

DOI:10.1038/s41598-021-85964-2
PMID:33762596
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7990972/
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 AuNP. 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 Au.

摘要

金纳米粒子(AuNP)的剂量增强作用增加了生物分子和组织中辐射损伤的生物学效应。为了在癌症治疗中有效地应用它们,必须确定它们对局部传递剂量的影响。在这里,AuNP 的位置强烈影响靶向细胞的核、线粒体、膜和细胞质中的能量沉积。为了估计这些影响,应用了粒子散射模拟。一般来说,对于 AuNP 及其在细胞内分布的建模,有不同的方法。在这项工作中,提出了两种新的连续和离散几何模型,用于模拟细胞内的 AuNP。这些模型适用于内部发射体和外部辐射源的模拟。目前大多数关于 AuNP 的研究都集中在外部束治疗上。相比之下,我们将提出的模型应用于蒙特卡罗粒子散射模拟中,以通过放射性 AuNP 来表征细胞细胞器中的能量沉积。它们发射β和γ射线,因此被认为适用于实体肿瘤的应用。随机分布和核靶向纳米粒子之间局部剂量增强的差异进行了比较。在这里,核靶向纳米粒子在放射性敏感的核中表现出强烈的局部剂量增强。这些结果是未来实验工作的基础,旨在获得放射性 Au 诱导细胞死亡的机制理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4cb/7990972/79d115986a64/41598_2021_85964_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4cb/7990972/27cac4261ae8/41598_2021_85964_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4cb/7990972/ddbc5090e0fb/41598_2021_85964_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4cb/7990972/c00ee8ca7253/41598_2021_85964_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4cb/7990972/79d115986a64/41598_2021_85964_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4cb/7990972/27cac4261ae8/41598_2021_85964_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4cb/7990972/ddbc5090e0fb/41598_2021_85964_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4cb/7990972/c00ee8ca7253/41598_2021_85964_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4cb/7990972/79d115986a64/41598_2021_85964_Fig4_HTML.jpg

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