Application of High-Z Gold Nanoparticles in Targeted Cancer Radiotherapy-Pharmacokinetic Modeling, Monte Carlo Simulation and Radiobiological Effect Modeling.
Application of High-Z Gold Nanoparticles in Targeted Cancer Radiotherapy-Pharmacokinetic Modeling, Monte Carlo Simulation and Radiobiological Effect Modeling.
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DOI：
10.3390/cancers13215370
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发表时间：
2021-10-26
期刊：
影响因子：
5.2
通讯作者：
Multhoff G
中科院分区：
文献类型：
--
作者：
Li WB;Stangl S;Klapproth A;Shevtsov M;Hernandez A;Kimm MA;Schuemann J;Qiu R;Michalke B;Bernal MA;Li J;Hürkamp K;Zhang Y;Multhoff G
高Z金纳米粒子在癌症放射治疗中显示出潜在的放射增敏剂。在本文中，我们介绍了金纳米粒子在靶向癌症放射治疗中的应用的好处和程序。基于抗体偶联纳米颗粒分布的显微图像，我们建立了模拟临床前模型中纳米颗粒偶联物在肿瘤和肿瘤环境中的生物分布的药代动力学模型。这一信息已在辐射输运蒙特卡罗模拟代码中实现，用于进一步研究物理和化学增强和放射生物学效应，如DNA链断裂和细胞存活。还讨论了将这种有前途的金纳米颗粒辅助放射治疗转化为临床实践的未来前景和挑战。与靶向抗体结合的高Z金纳米颗粒（AuNPs）可以帮助改善放射治疗中的肿瘤控制，同时最大限度地减少对邻近健康组织的放射毒性。本文总结了一项联合研究计划的主要结果，该计划将金纳米粒子结合物应用于临床前放射治疗建模，该研究在慕尼黑技术大学和亥姆霍兹慕尼黑中心进行。开发了超顺磁性氧化铁纳米颗粒的药代动力学模型，为模拟小鼠中AuNPs的摄取和分布的模型做准备。在细胞和分子水平上对肿瘤细胞中的单个AuNP和多个AuNP进行多尺度蒙特卡罗模拟，以确定辐射剂量的增强和与AuNP紧密接近的化学自由基的产生。建立了一个基于生物学的数学模型来预测金纳米粒子在辐射增强中的生物学响应。虽然单个AuNP的模拟显示出明显的剂量增强，但与化学自由基的产生和由多个AuNP诱导的DNA链断裂的诱导相关的模拟仅显示出较小的剂量增强。在分子和细胞水平上模拟增强的差异表明，在将这些AuNPs模型转化为靶向癌症放疗之前，有必要进行进一步的研究，以更好地了解临床前实验环境中物理，化学和生物学参数的影响。
High-Z gold nanoparticles show potential as radiosensitizers in the radiotherapy of cancer. In this paper, we introduce the benefits and procedures for the application of gold nanoparticles in targeted cancer radiotherapy. Based on microscopic images of the distribution of antibody-conjugated nanoparticles, we established pharmacokinetic models simulating the biodistribution of nanoparticle conjugates in the tumor and tumor environment in preclinical models. This information has been implemented in radiation transport Monte Carlo simulation codes for further investigating physical and chemical enhancement and radiobiological effects, such as DNA strand breaks and cell survival. Future perspectives and challenges of translating this promising gold nanoparticle-aided radiotherapy into clinical practice are also discussed. High-Z gold nanoparticles (AuNPs) conjugated to a targeting antibody can help to improve tumor control in radiotherapy while simultaneously minimizing radiotoxicity to adjacent healthy tissue. This paper summarizes the main findings of a joint research program which applied AuNP-conjugates in preclinical modeling of radiotherapy at the Klinikum rechts der Isar, Technical University of Munich and Helmholtz Zentrum München. A pharmacokinetic model of superparamagnetic iron oxide nanoparticles was developed in preparation for a model simulating the uptake and distribution of AuNPs in mice. Multi-scale Monte Carlo simulations were performed on a single AuNP and multiple AuNPs in tumor cells at cellular and molecular levels to determine enhancements in the radiation dose and generation of chemical radicals in close proximity to AuNPs. A biologically based mathematical model was developed to predict the biological response of AuNPs in radiation enhancement. Although simulations of a single AuNP demonstrated a clear dose enhancement, simulations relating to the generation of chemical radicals and the induction of DNA strand breaks induced by multiple AuNPs showed only a minor dose enhancement. The differences in the simulated enhancements at molecular and cellular levels indicate that further investigations are necessary to better understand the impact of the physical, chemical, and biological parameters in preclinical experimental settings prior to a translation of these AuNPs models into targeted cancer radiotherapy.
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影响因子：
5.5
作者：
Cooper DR;Bekah D;Nadeau JL
通讯作者：
Nadeau JL
影响因子：
5.7
作者：
Brown JMC;Currell FJ
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Currell FJ
影响因子：
3.5
作者：
Cho, SH
通讯作者：
Cho, SH
影响因子：
3.8
作者：
Bernal, M. A.;deAlmeida, C. E.;Nieminen, P.
通讯作者：
Nieminen, P.
影响因子：
5.4
作者：
Caro C;Gámez F;Quaresma P;Páez-Muñoz JM;Domínguez A;Pearson JR;Pernía Leal M;Beltrán AM;Fernandez-Afonso Y;De la Fuente JM;Franco R;Pereira E;García-Martín ML
通讯作者：
García-Martín ML