Department of Medical Biophysics, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario M4N3M5, Canada.
Phys Med Biol. 2011 Aug 7;56(15):4631-47. doi: 10.1088/0031-9155/56/15/001. Epub 2011 Jul 6.
Gold nanoparticle (AuNP) radiosensitization represents a novel approach to enhance the effectiveness of ionizing radiation. Its efficiency varies widely with photon source energy and AuNP size, concentration, and intracellular localization. In this Monte Carlo study we explored the effects of those parameters to define the optimal clinical use of AuNPs. Photon sources included (103)Pd and (125)I brachytherapy seeds; (169)Yb, (192)Ir high dose rate sources, and external beam sources 300 kVp and 6 MV. AuNP sizes were 1.9, 5, 30, and 100 nm. We observed a 10(3) increase in the rate of photoelectric absorption using (125)I compared to 6 MV. For a (125)I source, to double the dose requires concentrations of 5.33-6.26 mg g(-1) of Au or 7.10 × 10(4) 30 nm AuNPs per tumor cell. For 6 MV, concentrations of 1560-1760 mg g(-1) or 2.17 × 10(7) 30 nm AuNPs per cell are needed, which is not clinically achievable. Examining the proportion of energy transferred to escaping particles or internally absorbed in the nanoparticle suggests two clinical strategies: the first uses photon energies below the k-edge and takes advantage of the extremely localized Auger cascade. It requires small AuNPs conjugated to tumor targeted moieties and nuclear localizing sequences. The second, using photon sources above the k-edge, requires a higher gold concentration in the tumor region. In this approach, energy deposited by photoelectrons is the main contribution to radiosensitization; AuNP size and cellular localization are less relevant.
金纳米颗粒（AuNP）增敏代表了一种提高电离辐射有效性的新方法。其效率随光子源能量和 AuNP 尺寸、浓度以及细胞内定位而有很大差异。在这项蒙特卡罗研究中，我们探讨了这些参数的影响，以确定 AuNP 临床应用的最佳条件。光子源包括（103）Pd 和（125）I 近距离放疗种子；（169）Yb、（192）Ir 高剂量率源以及 300 kVp 和 6 MV 外照射源。AuNP 尺寸分别为 1.9、5、30 和 100nm。与 6 MV 相比，（125）I 使光电吸收速率提高了 103 倍。对于（125）I 源，要使剂量加倍，需要 Au 的浓度为 5.33-6.26mg g-1 或每个肿瘤细胞 7.10×104 个 30nm AuNP。对于 6 MV，需要 Au 的浓度为 1560-1760mg g-1 或每个细胞 2.17×107 个 30nm AuNP，这在临床上是无法实现的。考察转移到逃逸粒子的能量比例或纳米颗粒内的内部吸收能量表明了两种临床策略：第一种方法使用低于 K 边的光子能量，并利用极其局部化的俄歇级联。它需要将与肿瘤靶向部分和核定位序列结合的小 AuNP。第二种方法使用 K 边以上的光子源，需要在肿瘤区域内有更高的金浓度。在这种方法中，光电子沉积的能量是放射增敏的主要贡献；AuNP 尺寸和细胞定位的相关性较小。
