Application of High-Z Gold Nanoparticles in Targeted Cancer Radiotherapy—Pharmacokinetic Modeling, Monte Carlo Simulation and Radiobiological Effect Modeling

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 precli...

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Autores principales:	Wei Bo Li, Stefan Stangl, Alexander Klapproth, Maxim Shevtsov, Alicia Hernandez, Melanie A. Kimm, Jan Schuemann, Rui Qiu, Bernhard Michalke, Mario A. Bernal, Junli Li, Kerstin Hürkamp, Yibao Zhang, Gabriele Multhoff
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	cancers gold nanoparticles X-rays cmHsp70.1 conjugation targeted radiotherapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/873298103d0c414da86571d8be331310
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spelling	oai:doaj.org-article:873298103d0c414da86571d8be3313102021-11-11T15:29:24ZApplication of High-Z Gold Nanoparticles in Targeted Cancer Radiotherapy—Pharmacokinetic Modeling, Monte Carlo Simulation and Radiobiological Effect Modeling10.3390/cancers132153702072-6694https://doaj.org/article/873298103d0c414da86571d8be3313102021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5370https://doaj.org/toc/2072-6694High-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.Wei Bo LiStefan StanglAlexander KlapprothMaxim ShevtsovAlicia HernandezMelanie A. KimmJan SchuemannRui QiuBernhard MichalkeMario A. BernalJunli LiKerstin HürkampYibao ZhangGabriele MulthoffMDPI AGarticlecancersgold nanoparticlesX-rayscmHsp70.1conjugationtargeted radiotherapyNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5370, p 5370 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cancers gold nanoparticles X-rays cmHsp70.1 conjugation targeted radiotherapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	cancers gold nanoparticles X-rays cmHsp70.1 conjugation targeted radiotherapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Wei Bo Li Stefan Stangl Alexander Klapproth Maxim Shevtsov Alicia Hernandez Melanie A. Kimm Jan Schuemann Rui Qiu Bernhard Michalke Mario A. Bernal Junli Li Kerstin Hürkamp Yibao Zhang Gabriele Multhoff Application of High-Z Gold Nanoparticles in Targeted Cancer Radiotherapy—Pharmacokinetic Modeling, Monte Carlo Simulation and Radiobiological Effect Modeling
description	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.
format	article
author	Wei Bo Li Stefan Stangl Alexander Klapproth Maxim Shevtsov Alicia Hernandez Melanie A. Kimm Jan Schuemann Rui Qiu Bernhard Michalke Mario A. Bernal Junli Li Kerstin Hürkamp Yibao Zhang Gabriele Multhoff
author_facet	Wei Bo Li Stefan Stangl Alexander Klapproth Maxim Shevtsov Alicia Hernandez Melanie A. Kimm Jan Schuemann Rui Qiu Bernhard Michalke Mario A. Bernal Junli Li Kerstin Hürkamp Yibao Zhang Gabriele Multhoff
author_sort	Wei Bo Li
title	Application of High-Z Gold Nanoparticles in Targeted Cancer Radiotherapy—Pharmacokinetic Modeling, Monte Carlo Simulation and Radiobiological Effect Modeling
title_short	Application of High-Z Gold Nanoparticles in Targeted Cancer Radiotherapy—Pharmacokinetic Modeling, Monte Carlo Simulation and Radiobiological Effect Modeling
title_full	Application of High-Z Gold Nanoparticles in Targeted Cancer Radiotherapy—Pharmacokinetic Modeling, Monte Carlo Simulation and Radiobiological Effect Modeling
title_fullStr	Application of High-Z Gold Nanoparticles in Targeted Cancer Radiotherapy—Pharmacokinetic Modeling, Monte Carlo Simulation and Radiobiological Effect Modeling
title_full_unstemmed	Application of High-Z Gold Nanoparticles in Targeted Cancer Radiotherapy—Pharmacokinetic Modeling, Monte Carlo Simulation and Radiobiological Effect Modeling
title_sort	application of high-z gold nanoparticles in targeted cancer radiotherapy—pharmacokinetic modeling, monte carlo simulation and radiobiological effect modeling
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/873298103d0c414da86571d8be331310
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Application of High-Z Gold Nanoparticles in Targeted Cancer Radiotherapy—Pharmacokinetic Modeling, Monte Carlo Simulation and Radiobiological Effect Modeling

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