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

Abstract

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.

Review of the Geant4-DNA Simulation Toolkit for Radiobiological Applications at the Cellular and DNA Level

“…Furthermore, material that is specific cross sections for biopolymers [ 51 ] and for gold [ 143 , 144 ] that are used in nanodosimetry have already been developed and tested and they are soon going to be made available to the scientific community through Geant4-DNA. Especially, the cross sections for gold can contribute significantly to the gold nanoparticle-aided radiotherapy research [ 145 , 146 ]. The modeling of the chemical stage is currently being improved [ 133 ] and extended to longer times and macroscopic volumes [ 147 ].…”

Recent Advances in Copper-Based Organic Complexes and Nanoparticles for Tumor Theranostics

“…In recent years, with the continuous in-depth research of nanomaterials compared with traditional antitumor treatments, nanomaterials have been used in more and more clinical anticancer applications, showing great development potential [ 111 ]. For example, in our previous research, we found that some nanoparticles, such as superparamagnetic iron oxide nanoparticles (SPIONs), high-Z gold nanoparticles following intratumoral injection can provide a high local concentration of the agent, reduction of the particle clearance (i.e., renal or hepatic clearance) that increases the bioavailability of nanoparticles and has the effect of radiosensitizer in cancer radiotherapy, which can be used for long-term local anti-tumor therapy [ 112 , 113 ]. As an ideal anti-tumor drug candidate, copper-based nanomaterials have the following advantages: (i) compared with other metals, copper is cheap and rich in content [ 114 ], (ii) copper can induce reactive oxygen species (ROS)-mediated oxidative stress and promote tumor cell apoptosis [ 115 , 116 , 117 ], (iii) it has good biocompatibility, biodegradability, antibacterial properties, and selective cytotoxicity to cancer cells [ 118 ], and (iv) copper-based nanomaterials have less toxic effects on normal cells, fewer side effects, and are safer and more reliable [ 119 ].…”

Scientific Basics of Personalized Medicine: Realities and Opportunities

“…To evaluate the behavior of nanoparticles in vivo, we developed a pharmacokinetic model that mimics the uptake and distribution of AuNPs in mice. Multiscale Monte Carlo simulations were performed for AuNPs and SPIONs in tumor cells at the cellular and molecular levels to determine the increase in radiation dose and the formation of chemical radicals in the vicinity of AuNPs [ 17 ]. A biologically based mathematical model has been developed to predict the biological response of AuNPs to radiation amplification.…”