Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario M5S 3M2, Canada.
Med Phys. 2013 Nov;40(11):114101. doi: 10.1118/1.4823787.
The authors' aims were to model how various factors influence radiation dose enhancement by gold nanoparticles (AuNPs) and to propose a new modeling approach to the dose enhancement factor (DEF).
The authors used Monte Carlo N-particle (MCNP 5) computer code to simulate photon and electron transport in cells. The authors modeled human breast cancer cells as a single cell, a monolayer, or a cluster of cells. Different numbers of 5, 30, or 50 nm AuNPs were placed in the extracellular space, on the cell surface, in the cytoplasm, or in the nucleus. Photon sources examined in the simulation included nine monoenergetic x-rays (10-100 keV), an x-ray beam (100 kVp), and (125)I and (103)Pd brachytherapy seeds. Both nuclear and cellular dose enhancement factors (NDEFs, CDEFs) were calculated. The ability of these metrics to predict the experimental DEF based on the clonogenic survival of MDA-MB-361 human breast cancer cells exposed to AuNPs and x-rays were compared.
NDEFs show a strong dependence on photon energies with peaks at 15, 30/40, and 90 keV. Cell model and subcellular location of AuNPs influence the peak position and value of NDEF. NDEFs decrease in the order of AuNPs in the nucleus, cytoplasm, cell membrane, and extracellular space. NDEFs also decrease in the order of AuNPs in a cell cluster, monolayer, and single cell if the photon energy is larger than 20 keV. NDEFs depend linearly on the number of AuNPs per cell. Similar trends were observed for CDEFs. NDEFs using the monolayer cell model were more predictive than either single cell or cluster cell models of the DEFs experimentally derived from the clonogenic survival of cells cultured as a monolayer. The amount of AuNPs required to double the prescribed dose in terms of mg Au/g tissue decreases as the size of AuNPs increases, especially when AuNPs are in the nucleus and the cytoplasm. For 40 keV x-rays and a cluster of cells, to double the prescribed x-ray dose (NDEF = 2) using 30 nm AuNPs, would require 5.1 ± 0.2, 9 ± 1, 10 ± 1, 10 ± 1 mg Au/g tissue in the nucleus, in the cytoplasm, on the cell surface, or in the extracellular space, respectively. Using 50 nm AuNPs, the required amount decreases to 3.1 ± 0.3, 8 ± 1, 9 ± 1, 9 ± 1 mg Au/g tissue, respectively.
NDEF is a new metric that can predict the radiation enhancement of AuNPs for various experimental conditions. Cell model, the subcellular location and size of AuNPs, and the number of AuNPs per cell, as well as the x-ray photon energy all have effects on NDEFs. Larger AuNPs in the nucleus of cluster cells exposed to x-rays of 15 or 40 keV maximize NDEFs.
作者旨在模拟各种因素如何影响金纳米粒子（AuNP）的辐射剂量增强，并提出一种新的剂量增强因子（DEF）建模方法。
作者使用蒙特卡罗 N 粒子（MCNP5）计算机代码模拟光子和电子在细胞中的输运。作者将人乳腺癌细胞建模为单个细胞、单层或细胞簇。不同数量的 5、30 或 50nm AuNP 分别置于细胞外空间、细胞膜表面、细胞质或细胞核中。模拟中检查的光子源包括 9 种单能 X 射线（10-100keV）、X 射线束（100kVp）和（125）I 和（103）Pd 近距离治疗种子。计算了核和细胞剂量增强因子（NDEFs、CDEFs）。比较了这些指标基于 MDA-MB-361 人乳腺癌细胞暴露于 AuNP 和 X 射线后的克隆存活，预测实验 DEF 的能力。
NDEF 对光子能量具有很强的依赖性，在 15、30/40 和 90keV 处出现峰值。AuNP 的细胞模型和亚细胞位置影响 NDEF 的峰值位置和值。NDEF 按 AuNP 在核、细胞质、细胞膜和细胞外空间中的顺序递减。如果光子能量大于 20keV，NDEF 也按 AuNP 在细胞簇、单层和单个细胞中的顺序递减。NDEF 与每个细胞中的 AuNP 数量呈线性关系。在从单层细胞培养的细胞克隆存活中实验得出的 DEF 方面，CDEF 也表现出类似的趋势。使用单层细胞模型的 NDEF 比从单个细胞或细胞簇模型得出的 DEF 更具预测性。
NDEF 是一种新的指标，可以预测各种实验条件下 AuNP 的辐射增强。细胞模型、AuNP 的亚细胞位置和大小以及每个细胞中的 AuNP 数量以及 X 射线光子能量都对 NDEF 有影响。在 15 或 40keV X 射线照射下，簇细胞中较大的核内 AuNP 最大限度地提高了 NDEF。
