Microdosimetric Investigation and a Novel Model of Radiosensitization in the Presence of Metallic Nanoparticles.
Microdosimetric Investigation and a Novel Model of Radiosensitization in the Presence of Metallic Nanoparticles.
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DOI：
10.3390/pharmaceutics13122191
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发表时间：
2021-12-18
期刊：
影响因子：
5.4
通讯作者：
Liu W
中科院分区：
文献类型：
--
作者：
Yan H;Carlson DJ;Abolfath R;Liu W
电离后高原子序数纳米粒子 (NP) 中产生的俄歇级联被认为是 NP 放射增敏的潜在机制。在这项工作中，我们使用双辐射作用理论 (TDRA) 研究了俄歇级联的微剂量后果，并提出了新颖的炸弹模型作为描述 NP 相关放射增敏的通用框架。当被电离事件触发时，炸弹模型会考虑靠近辐射敏感细胞目标的纳米粒子，产生密集的二次电子并根据概率分布杀死细胞，就像“炸弹”一样。 TDRA加距离模型被用作计算线性二次生存模型的α变化和相对生物有效性（RBE）的理论基础。我们分别计算了在钆基纳米粒子 (AGuIXTM) 存在的 250 kVp X 射线照射下和在 50 nm 金纳米粒子 (AuNP) 存在的 220 kVp X 射线照射下 SQ20B 和 Hela 人类癌细胞的这些量，并与现有的实验数据进行了比较。基于 Geant4 的蒙特卡罗 (MC) 模拟用于 (1) 生成进入 NP 的光子的电子能谱和相空间数据，以及 (2) 计算 TDRA 和炸弹模型的邻近函数和其他相关参数。俄歇级联电子的邻近函数比水中的光电电子和康普顿电子高出 30%，但由此产生的 α 增量小于实验数据得出的增量。计算的 RBE 无法解释实验结果。在 250 kVp X 射线照射下，使用 AGuIX 的 SQ20B 细胞的 TDRA 预测的 α 相对增加比实验结果低至少 45 倍，在 220 kVp X 射线照射下使用 AuNP 的 Hela 细胞则至少低 4 倍。在 220 kVp X 射线照射下，将炸弹模型应用于具有 AuNP 的 Hela 细胞表明，由较高能量光子引起的 NP 的单一电离事件具有更高的杀死细胞的可能性。靠近细胞核的纳米粒子对放射增敏更有效。俄歇电子级联细胞死亡的 RBE 微剂量计算无法解释实验观察到的 AGuIX 或 AuNP 的放射增敏作用，而所提出的炸弹模型是描述低 NP 浓度下与 NP 相关的放射增敏作用的潜在候选模型。
Auger cascades generated in high atomic number nanoparticles (NPs) following ionization were considered a potential mechanism for NP radiosensitization. In this work, we investigated the microdosimetric consequences of the Auger cascades using the theory of dual radiation action (TDRA), and we propose the novel Bomb model as a general framework for describing NP-related radiosensitization. When triggered by an ionization event, the Bomb model considers the NPs that are close to a radiation sensitive cellular target, generates dense secondary electrons and kills the cells according to a probability distribution, acting like a “bomb.” TDRA plus a distance model were used as the theoretical basis for calculating the change in α of the linear-quadratic survival model and the relative biological effectiveness (RBE). We calculated these quantities for SQ20B and Hela human cancer cells under 250 kVp X-ray irradiation with the presence of gadolinium-based NPs (AGuIXTM), and 220 kVp X-ray irradiation with the presence of 50 nm gold NPs (AuNPs), respectively, and compared with existing experimental data. Geant4-based Monte Carlo (MC) simulations were used to (1) generate the electron spectrum and the phase space data of photons entering the NPs and (2) calculate the proximity functions and other related parameters for the TDRA and the Bomb model. The Auger cascade electrons had a greater proximity function than photoelectric and Compton electrons in water by up to 30%, but the resulting increases in α were smaller than those derived from experimental data. The calculated RBEs cannot explain the experimental findings. The relative increase in α predicted by TDRA was lower than the experimental result by a factor of at least 45 for SQ20B cells with AGuIX under 250 kVp X-ray irradiation, and at least four for Hela cells with AuNPs under 220 kVp X-ray irradiation. The application of the Bomb model to Hela cells with AuNPs under 220 kVp X-ray irradiation indicated that a single ionization event for NPs caused by higher energy photons has a higher probability of killing a cell. NPs that are closer to the cell nucleus are more effective for radiosensitization. Microdosimetric calculations of the RBE for cell death of the Auger electron cascade cannot explain the experimentally observed radiosensitization by AGuIX or AuNP, while the proposed Bomb model is a potential candidate for describing NP-related radiosensitization at low NP concentrations.
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影响因子：
3.8
作者：
BORLE, AB
通讯作者：
BORLE, AB
影响因子：
3.4
作者：
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作者：
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3.8
作者：
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通讯作者：
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影响因子：
2.6
作者：
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