Gold Nanoparticles In Radiotherapy Research Articles

Dosimetric Impact on the Flattening Filter and Addition of Gold Nanoparticles in Radiotherapy: A Monte Carlo Study on Depth Dose Using the 6 and 10 MV FFF Photon Beams.

Purpose: This phantom study investigated through Monte Carlo simulation how the dose enhancement varied with depth, when gold nanoparticles (NPs) were added using the flattening filter-free (FFF) photon beams in gold NP-enhanced radiotherapy. Method: A phantom with materials varying from pure water to a mixture of water and gold NPs at different concentrations (3–40 mg/mL) were irradiated by the 6 and 10 MV flattening filter (FF) and FFF photon beams. Monte Carlo simulations were carried out to determine the depth doses along the central beam axis of the phantom up to a depth of 40 cm. The dose enhancement ratio (DER) and FFF enhancement ratio (FFFER) were calculated based on the Monte Carlo results. Results: The DER values were found decreased with an increase of depth and increase of NP concentration in the phantom. For the maximum NP concentration of 40 mg/mL, the DER values decreased 6.9, 12, 4.6 and 7.2% at a phantom depth from 2 to 40 cm, using the 6 MV FF, 6 MV FFF, 10 MV FF and 10 MV FFF photon beams, respectively. The maximum DER values for the 6 MV beams were 1.08 (FF) and 1.14 (FFF), while those for the 10 MV beams were 1.04 (FF) and 1.07 (FFF). When the FF was removed from the linear accelerator head, the FFFER showed a more significant increase of dose enhancement for the 6 MV beams (1.057) than the 10 MV (1.031). Conclusion: From the DER and FFFER values based on the Monte Carlo results, it is concluded that the dose enhancement with depth was dependent on the NP and beam variables, namely, NP concentration, presence of FF in the beam and beam energy. Dose enhancement was more significant when using the lower photon beam energy (i.e., 6 MV), FFF photon beam and higher NP concentration in the study.

Albumin stabilized Pt nanoparticles as radiosensitizer for sensitization of breast cancer cells under X-ray radiation therapy

The purpose of this study is to synthesize and assess the platinum nanoparticles (Pt NPs) coated with bovine serum albumin (BSA), [email protected] NPs, as a potential radiosensitizer that may be used in radiotherapy to improve the efficiency of X-ray therapy. Pt NPs with a high atomic number have the potential to be a competitive alternative to gold nanoparticles in radiotherapy. Besides, BSA not only exhibited a stabilizing effect, but it also served as a safe cradle for platinum nanoparticles that were escaping from the reticuloendothelial system during blood circulation. Furthermore, physical and chemical properties of [email protected] NPs also characterized by TEM, UV–Vis, FTIR, SEM and DLS. Then, the biocompatibility of [email protected] NPs was investigated using hemolysis test. Finally, the prepared NPs at different concentrations were adjacent to 4 T1 cells and its efficacy in the presence and absence of X-rays was studied. NPs show average diameter of 6.64 ± 1.3 nm in TEM image and 29.4 nm hydrodynamic size which achieved from DLS result. Moreover, the NPs show negative surface charge, −29.3 mv. Breast cancer cells experience greater toxicity in the simultaneous presence of nanoparticles and X-rays.

Gold Nanoparticles in Radiotherapy and Recent Progress in Nanobrachytherapy.

Over the last few decades, gold nanoparticles (GNPs) have emerged as "radiosensitizers" in oncology. Radiosensitizers are additives that can enhance the effects of radiation on biological tissues treated with radiotherapy. The interaction of photons with GNPs leads to the emission of low-energy and short-range secondary electrons, which in turn increase the dose deposited in tissues. In this context, GNPs are the subject of intensive theoretical and experimental studies aiming at optimizing the parameters leading to greater dose enhancement and highest therapeutic effect. This review describes the main mechanisms occurring between photons and GNPs that lead to dose enhancement. The outcome of theoretical simulations of the interactions between GNPs and photons is presented. Finally, the findings of the most recent in vivo studies about interactions between GNPs and photon sources (e.g., external beams, brachytherapy sources, and molecules labeled with radioisotopes) are described. The advantages and challenges inherent to each of these approaches are discussed. Future directions, providing new guidelines for the successful translation of GNPs into clinical applications, are also highlighted.

Geant4-DNA track-structure simulations for gold nanoparticles: The importance of electron discrete models in nanometer volumes.

Gold nanoparticles (GNPs) are known to enhance the absorbed dose in their vicinity following photon-based irradiation. To investigate the therapeutic effectiveness of GNPs, previous Monte Carlo simulation studies have explored GNP dose enhancement using mostly condensed-history models. However, in general, such models are suitable for macroscopic volumes and for electron energies above a few hundred electron volts. We have recently developed, for the Geant4-DNA extension of the Geant4 Monte Carlo simulation toolkit, discrete physics models for electron transport in gold which include the description of the full atomic de-excitation cascade. These models allow event-by-event simulation of electron tracks in gold down to 10eV. The present work describes how such specialized physics models impact simulation-based studies on GNP-radioenhancement in a context of x-ray radiotherapy. The new discrete physics models are compared to the Geant4 Penelope and Livermore condensed-history models, which are being widely used for simulation-based NP radioenhancement studies. An ad hoc Geant4 simulation application has been developed to calculate the absorbed dose in liquid water around a GNP and its radioenhancement, caused by secondary particles emitted from the GNP itself, when irradiated with a monoenergetic electron beam. The effect of the new physics models is also quantified in the calculation of secondary particle spectra, when originating in the GNP and when exiting from it. The new physics models show similar backscattering coefficients with the existing Geant4 Livermore and Penelope models in large volumes for 100keV incident electrons. However, in submicron sized volumes, only the discrete models describe the high backscattering that should still be present around GNPs at these length scales. Sizeable differences (mostly above a factor of 2) are also found in the radial distribution of absorbed dose and secondary particles between the new and the existing Geant4 models. The degree to which these differences are due to intrinsic limitations of the condensed-history models or to differences in the underling scattering cross sections requires further investigation. Improved physics models for gold are necessary to better model the impact of GNPs in radiotherapy via Monte Carlo simulations. We implemented discrete electron transport models for gold in Geant4 that is applicable down to 10eV including the modeling of the full de-excitation cascade. It is demonstrated that the new model has a significant positive impact on particle transport simulations in gold volumes with submicron dimensions compared to the existing Livermore and Penelope condensed-history models of Geant4.

A Monte Carlo Study on Dose Enhancement by Homogeneous and Inhomogeneous Distributions of Gold Nanoparticles in Radiotherapy with Low Energy X-rays.

To enhance the dose to tumor, the use of high atomic number elements has been proposed. The aim of this study is to investigate the effect of gold nanoparticle distribution on dose enhancement in tumor when the tumor is irradiated by typical monoenergetic X-ray beams by considering homogeneous and inhomogeneous distributions of gold nanoparticles (GNPs) in the tumor. MCNP-4C Monte Carlo code was utilized for the simulation of a source, a phantom containing tumor and gold nanoparticles with concentrations of 10, 30 and 70 mg Au/g tumor. A 15 cm×15 cm×15 cm cubic water phantom was irradiated with a small planar source with four monoenergetic X-ray beams of 35, 55, 75 and 95 keV energy. Furthermore, tumor depths of 2.5 cm, 4.5 cm and 6.5 cm with homogeneous and inhomogeneous distributions of nanoparticles were studied. Each concentration, photon energy, tumor depth and type of distribution was evaluated in a separate simulation. Results have shown that dose enhancement factor (DEF) in tumor increases approximately linearly with the concentration of gold nanoparticles. While DEF has fluctuations with photon energy, 55 keV photons have the highest DEF values compared to other energies. While DEF has relatively the same values with tumor located at various depths, inhomogeneous distribution of GNP has shown different results compared with the homogeneous model. Dose enhancement can be expected with relatively deep seated tumors in radiotherapy with low energy X-rays. Inhomogeneous model is recommended for the purpose of dose enhancement study because it mimics the real distribution of GNPs in tumor.

Targeting integrins with RGD-conjugated gold nanoparticles in radiotherapy decreases the invasive activity of breast cancer cells.

Gold nanoparticles (AuNPs) have recently attracted attention as clinical agents for enhancing the effect of radiotherapy in various cancers. Although radiotherapy is a standard treatment for cancers, invasive recurrence and metastasis are significant clinical problems. Several studies have suggested that radiation promotes the invasion of cancer cells by activating molecular mechanisms involving integrin and fibronectin (FN). In this study, polyethylene-glycolylated AuNPs (P-AuNPs) were conjugated with Arg–Gly–Asp (RGD) peptides (RGD/P-AuNPs) to target cancer cells expressing RGD-binding integrins such as α5- and αv-integrins. RGD/P-AuNPs were internalized more efficiently and colocalized with integrins in the late endosomes and lysosomes of MDA-MB-231 cells. A combination of RGD/P-AuNPs and radiation reduced cancer cell viability and increased DNA damage compared to radiation alone in MDA-MB-231 cells. Moreover, the invasive activity of breast cancer cell lines after radiation treatment was significantly inhibited in the presence of RGD/P-AuNPs. Microarray analyses revealed that the expression of FN in irradiated cells was suppressed by combined use of RGD/P-AuNPs. Reduction of FN and downstream signaling may be involved in suppressing radiation-induced invasive activity by RGD/P-AuNPs. Our study suggests that RGD/P-AuNPs can target integrin-overexpressing cancer cells to improve radiation therapy by suppressing invasive activity in addition to sensitization. Thus, these findings provide a possible clinical strategy for using AuNPs to treat invasive breast cancer following radiotherapy.

EP-1917: Measurements of reactive oxygen species production induced by gold nanoparticles in radiotherapy

EP-1917: Measurements of reactive oxygen species production induced by gold nanoparticles in radiotherapy

Preparation, physicochemical characterization and performance evaluation of gold nanoparticles in radiotherapy.

The aim of the present study was preparation, physicochemical characterization and performance evaluation of gold nanoparticles (GNPs) in radiotherapy. Another objective was the investigation of anti-bacterial efficacy of gold nanoparticle against E. coli clinical strains. Gold nanoparticles prepared by controlled reduction of an aqueous HAuCl4 solution using Tri sodium citrate. Particle size analysis and Transmission electron microscopy were used for physicochemical characterization. Polymer gel dosimetry was used for evaluation of the enhancement of absorbed dose. Diffusion method in agar media was used for investigation of anti-bacterial effect. Gold nanoparticles synthesized in size range from 57 nm to 346 nm by planning different formulation. Gold nanoparticle in 57 nm size increased radiation dose effectiveness with the magnitude of about 21 %. At the concentration of 400 ppm, Nano gold exhibited significant anti-bacterial effect against E. coli clinical strains. It is concluded that gold nanoparticles can be applied as dose enhancer in radiotherapy. The Investigation of anti-bacterial efficacy showed that gold nanoparticle had significant effect against E. coli clinical strains.