An Analysis of the Radiosensitiser Applications in the Biomedical Field.

BACKGROUND: Various types of radiosensitisers have been introduced from the past until the present day for applications in the biomedical field. However, there is a lack of understanding and comparison between the various parameters introduced in addition to a lack of consensus among researchers on the optimal radiosensitiser for applications in the biomedical field. OBJECTIVE: This review aimed to investigate the usage of radiosensitisers in the biomedical field, determine their important parameters, and suggest radiosensitisers with potential among the analysed radiosensitisers. RESULTS AND CONCLUSION: This review has discussed several parameters for radiosensitisers, including median lethal dose, cell survival, tumour size, cell viability, Dose Enhancement Factor (DEF), Reactive Oxygen Species (ROS) concentration, radiosensitiser production complexity, radiosensitiser administration technique, and radiosensitiser toxicity. General trends regarding the development of radiosensitisers, including the types, effectiveness, and their production complexity, have also been discussed within this review article.

Nanoscale dosimetry for a radioisotope-labeled metal nanoparticle using MCNP6.2 and Geant4.

BACKGROUND: Metal nanoparticles (MNPs) labeled with radioisotopes (RIs) are utilized as radio-enhancers due to their ability to amplify the radiation dose in their immediate vicinity. A thorough understanding of nanoscale dosimetry around MNPs enables their effective application in radiotherapy. However, nanoscale dosimetry around MNPs still requires further investigation. PURPOSE: This study aims to provide insight into the radio-enhancement effects of MNPs by elucidating nanoscale dosimetry surrounding MNPs labeled with Auger-emitting RIs. We particularly focus on distinguishing the respective dose contributions of photons and electrons emitted by Auger-emitting RIs in the context of dose enhancement. METHODS: A 50 nm diameter NP of silver (Ag) core and gold (Au) shell (Ag@Au NP) was assumed to emit mono-energetic electrons and photons (3, 5, 10, 20, and 30 keV), or the energy spectrum corresponding to one of three Auger-emitting RIs (103Pd, 125I, and 131Cs) from the Ag core. Nanoscale radial dose distributions around a single radioactive Ag@Au NP were evaluated in spherical shells of water. Monte Carlo simulations were conducted using single-event and track structure transport methods implemented in MCNP6.2 and Geant4-DNA-Au physics, respectively. To evaluate the extent of radio-enhancement by the Ag@Au NP, two scenarios were considered: Ag@Au NPs (Au shell included) and Ag@water NPs (Au shell replaced by water). RESULTS: The radial doses of 10, 20, and 30 keV electrons estimated by both codes were comparable. However, the radial doses of 3 and 5 keV electrons by MCNP6.2 were much larger near the NP surface than those by Geant4. There was a dose enhancement of a few % to tens % by the Au shell in the region of the NP surface to 10 µm, depending on the electron energy. The radial doses of photons with the Au shell were higher up to their secondary electron ranges than those without the Au shell. The maximum dose enhancement factor of photons occurred at 20 keV and was 63.4 by MCNP6.2 and 50.5 by Geant4. The overall radial doses of electrons were 1-2 orders of magnitude larger than those of photons. As a result, in cases of RIs emitting both electrons and photons, the radial doses up to electron ranges were dominantly governed by electrons. The dose enhancement estimated by both codes for the RIs ranged from a few % except in the immediate vicinity of the NP surface. CONCLUSION: Given the dominant contribution of electrons to radial doses of MNP labeled with Auger-emitting RIs, physical dose enhancement expected by interactions with photons was hindered. Since there are no available RIs emitting exclusively photons, achieving enhanced physical doses within a cell through a combination of MNPs and RIs appears currently unattainable. The radial doses of photons near the NP surface exhibited considerable discrepancies between the codes, primarily attributed to low-energy electrons. The difference may arise from higher cross-sections of Au inelastic scattering in Geant4-DNA-Au compared to MCNP6.2.

In vitro and in silico study of biological effects on cancer cells in the presence of metallic materials during radiotherapy.

X-ray therapy aims to eliminate tumours while minimizing side effects. Intense mucositis is sometimes induced when irradiating the oral cavity with a dental metal crown (DMC). However, the underlying mechanisms of such inducing radiosensitization by DMC remain uncertain. This study explored the radiosensitizing mechanisms around DMCs in an interdisciplinary approach with cell experiments and Monte Carlo simulation with the PHITS code. Clonogenic survival and nuclear 53BP1 foci of a cell line derived from cervical cancer cells (HeLa cells) were measured post-irradiation with therapeutic X-rays near high-Z materials such as Pb or Au plates, and the experimental sensitizer enhancement ratio (SER) was obtained. Meanwhile, the dose enhancement ratio (DER) and relative biological effectiveness for DNA damage yields were calculated using the PHITS code, by considering the corresponding experimental condition. The experiments show the experimental SER values for cell survival and 53BP1 foci near metals are 1.2-1.4, which agrees well with the calculated DER values. These suggest that the radiosensitizing effects near metal are predominantly attributed to the dose increase. In addition, as a preclinical evaluation, the spatial distributions of DER near DMC are calculated using Computed Tomography Digital Imaging and Communications in Medicine (CT-DICOM) data and a simple tooth model. As a result, the DER values evaluated using the CT-DICOM data were lower than those from a simple tooth model. These findings highlight the challenge of evaluating radiosensitizing effects near DMCs using Digital Imaging and Communications in Medicine (DICOM) images due to volume-averaging effects and emphasize the need for a high-resolution (<1 mm) dose assessment method unaffected by these effects.

Radiosensitization with metallic nanoparticles under MeV proton beams: local dose enhancement.

In addition to specific dosimetric properties of protons, their higher biological effectiveness makes them superior to X-rays and gamma radiation, in radiation therapy. In recent years, enrichment of tumours with metallic nanoparticles as radiosensitizer agents has generated high interest, with several studies attempting to confirm the efficacy of nanoparticles in proton therapy. In the present study Geant4 Monte Carlo (MC) code was used to quantify the increased nanoscopic dose deposition of 50 nm metallic nanoparticles including gold, bismuth, iridium, and gadolinium in water upon exposure to 5, 25, and 50 MeV protons. Dose enhancement factors, radial dose distributions in nano-scale, as well as secondary electron and photon energy spectra were calculated for the studied nanoparticles and proton beams. The obtained results demonstrated that in the presence of metallic nanoparticles an increase in proton energy leads to a decrease in secondary electron and photon production yield. Additionally, an increase in the radial dose enhancement factor from 1.4 to 16 was calculated for the studied nanoparticles when the proton energy was increased from 5 to 50 MeV. It is concluded that the dosimetric advantages of proton beams could be improved significantly in the presence of metallic nanoparticles.

A simulation study on the effect of penetration of gold nanoparticles in the cytoplasm of healthy eye organs on dose enhancement of brachytherapy.

PURPOSE: Special properties and recent advances in the synthesis and biomolecular functionalization of gold nanoparticles (GNPs) have led to the evolution of their use in biomedical applications such as photon radiotherapy. Simulation-based studies on the effect of various parameters that govern the dose enhancement due to utilizing GNPs have facilitated the progress of knowledge in this field. Due to their flexibility and easier accessibility compared with experimental works, simulations have the potential to be considered for pre-clinical tests and, therefore, should be close to the realistic conditions as much as possible. MATERIALS AND METHODS: To this aim, the present work investigates the effect of the presence of GNPs that are accumulated in the cytoplasm of the constituent cells in healthy tissues of a human eye phantom, inspired by the published experimental results which report that non-target tissues also receive the drugs containing GNPs. The GNPs' concentrations are assumed to decrease by moving from the tumor toward the depth of the phantom through a suggested pattern. The MCNPX Monte Carlo code is used for the simulations. RESULTS: The results show that for four concentrations tested, the dose enhancement factor in the shallower layer reaches 6, and decreases to 1.2 in the last layer. The dose enhancements are also examined for critical structures of the iris, cornea, sclera, and lens, showing maximum deviations of about 3 to 200% compared with the absence of GNPs in the healthy tissue. Considering the reported doses to the lens by clinical institutions, the effect of penetration of GNPs to deep layers on treatment time is also investigated. CONCLUSIONS: The results show that the penetration of GNPs from the tumor toward healthy tissues strongly controls the dose enhancement over the various eye structures and emphasizes the importance of modeling the GNPs' distribution in the medium on the overall dose enhancement. Considering the current challenges in the clinical use of GNPs, more effort needs to be made to reach an effective endpoint in treatment.

Enhanced radio-photodynamic therapy potential of advanced gold-based nanoclusters for breast cancer treatment.

The purpose of current study was to assess the impact of ALA-coated gold nanoclusters (Au NPs) on the combined therapeutic effects of radiotherapy (RT) and photodynamic therapy (PDT) on healthy MCF-10A and MCF-7 breast cancer cells. The Au NPs were covered with ALA using PEG polymer, resulting in the synthesis of Au@ALA NPs. The successful synthesis of the final NPs was confirmed through FTIR, XRD, TEM, and UV-Vis tests. MCF-10A and MCF-7 cell lines were treated with different concentrations of Au@ALA NPs and exposed to irradiation of 2 and 4 Gy (using MV X-ray) and 630 nm laser light irradiation. Cytotoxicity was assessed using a multifaceted approach involving the MTT assay, real-time PCR, and colony forming assay. The findings revealed that the damage inflicted by Au@ALA NPs on cancerous tissue was significantly greater than that on normal tissue. The cytotoxic effects of all experimental groups exhibited a direct correlation with increasing concentrations and radiation doses. The combination of Au@ALA NPs with RT doses of 2 and 4 Gy resulted in a reduction in cell viability by a factor of 1.58 (P = 0.001) and 1.73 (P = 0.004), respectively. Furthermore, the simultaneous intervention of NPs with PDT and RT at doses of 2 and 4 Gy led to a decrease in cell viability by a factor of 2.10 (P = 0.001) and 3.08 (P = 0.001) in turn. Furthermore, the real-time PCR and colonogenic assay results demonstrated that the combined treatment significantly increased phosphorylation of ATM and expression of TP53, indicating an adequate synergistic effect on breast cancer cells. The concurrent application of Au@ALA NPs in RT and PDT successfully enhanced the radiosensitization of breast cancer cells to megavoltage RT and PDT.

XMEA: A New Hybrid Diamond Multielectrode Array for the In Situ Assessment of the Radiation Dose Enhancement by Nanoparticles.

This work presents a novel multielectrode array (MEA) to quantitatively assess the dose enhancement factor (DEF) produced in a medium by embedded nanoparticles. The MEA has 16 nanocrystalline diamond electrodes (in a cell-culture well), and a single-crystal diamond divided into four quadrants for X-ray dosimetry. DEF was assessed in water solutions with up to a 1000 µg/mL concentration of silver, platinum, and gold nanoparticles. The X-ray detectors showed a linear response to radiation dose (r2 ≥ 0.9999). Overall, platinum and gold nanoparticles produced a dose enhancement in the medium (maximum of 1.9 and 3.1, respectively), while silver nanoparticles produced a shielding effect (maximum of 37%), lowering the dose in the medium. This work shows that the novel MEA can be a useful tool in the quantitative assessment of radiation dose enhancement due to nanoparticles. Together with its suitability for cells' exocytosis studies, it proves to be a highly versatile device for several applications.

An Optimized Method for Evaluating the Potential Gd-Nanoparticle Dose Enhancement Produced by Electronic Brachytherapy.

This work reports an optimized method to experimentally quantify the Gd-nanoparticle dose enhancement generated by electronic brachytherapy. The dose enhancement was evaluated considering energy beams of 50 kVp and 70 kVp, determining the Gd-nanoparticle concentration ranges that would optimize the process for each energy. The evaluation was performed using delaminated radiochromic films and a Poly(methyl methacrylate) (PMMA) phantom covered on one side by a thin 2.5 µm Mylar filter acting as an interface between the region with Gd suspension and the radiosensitive film substrate. The results for the 70 kVp beam quality showed dose increments of 6±6%, 22±7%, and 9±7% at different concentrations of 10, 20, and 30 mg/mL, respectively, verifying the competitive mechanisms of enhancement and attenuation. For the 50 kVp beam quality, no increase in dose was recorded for the concentrations studied, indicating that the major contribution to enhancement is from the K-edge interaction. In order to separate the contributions of attenuation and enhancement to the total dose, measurements were replicated with a 12 µm Mylar filter, obtaining a dose enhancement attributable to the K-edge of 29±7% and 34±7% at 20 and 30 mg/mL, respectively, evidencing a significant additional dose proportional to the Gd concentration.

Utility of realistic microscopy-based cell models in simulation studies of nanoparticle-enhanced photon radiotherapy.

To enhance the effect of radiation on the tumor without increasing the dose to the patient, the combination of high-Z nanoparticles with radiotherapy has been proposed. In this work, we investigate the effects of the physical parameters of nanoparticles (NPs) on the Dose Enhancement Factor (DEF), and on the Sensitive Enhancement Ratio (SER) by applying a version of the Linear Quadratic Model. A method for constructing voxelized realistic cell geometries in Monte Carlo simulations from confocal microscopy images was developed and applied to Gliobastoma Multiforme cell lines (U87 and U373). The comparison of simulations with realistic geometry and spherical geometry shows that there is significant impact on the survival curves obtained for the same irradiation conditions. Using this model, the DEF and the SER are determined as a function of the concentration, size and distribution of gold nanoparticles within the cell. For small NPs,dAuNP= 10 nm, no clear trend in the DEF and SER was observed when the number of NPs within the cell increases. Experimentally, the variable number of NPs measured inside the U373 cells (ranging between 1.48 × 105and 1.19 × 106) also did not influence much the observed cell survival upon irradiation of the cells with a Co-60 source. The same lack of trend is obtained when the Au content in the cell is kept constant, 0.897 mg/g, but the size of the NPs is changed. However, if the number of NPs is kept constant (7.91 × 105) and the size changes, there is a critical diameter above which the dose effect increases significantly. Using the realistic geometries, it was verified that the key parameter for the DEF and the SER enhancement is the volume fraction of Au in the cell, with NP size being a more important parameter than the number of NPs.

Synthesis and Bioapplication of Emerging Nanomaterials of Hafnium.

A significant amount of progress in nanotechnology has been made due to the development of engineered nanoparticles. The use of metallic nanoparticles for various biomedical applications has been extensively investigated. Biomedical research is highly focused on them because of their inert nature, nanoscale structure, and similar size to many biological molecules. The intrinsic characteristics of these particles, including electronic, optical, physicochemical, and surface plasmon resonance, that can be altered by altering their size, shape, environment, aspect ratio, ease of synthesis, and functionalization properties, have led to numerous biomedical applications. Targeted drug delivery, sensing, photothermal and photodynamic therapy, and imaging are some of these. The promising clinical results of NBTXR3, a high-Z radiosensitizing nanomaterial derived from hafnium, have demonstrated translational potential of this metal. This radiosensitization approach leverages the dependence of energy attenuation on atomic number to enhance energy-matter interactions conducive to radiation therapy. High-Z nanoparticle localization in tumor issue differentially increases the effect of ionizing radiation on cancer cells versus nearby healthy ones and mitigates adverse effects by reducing the overall radiation burden. This principle enables material multifunctionality as contrast agents in X-ray-based imaging. The physiochemical properties of hafnium (Z = 72) are particularly advantageous for these applications. A well-placed K-edge absorption energy and high mass attenuation coefficient compared to elements in human tissue across clinical energy ranges leads to significant attenuation. Chemical reactivity allows for variety in nanoparticle synthesis, composition, and functionalization. Nanoparticles such as hafnium oxide exhibit excellent biocompatibility due to physiochemical inertness prior to incidence with ionizing radiation. Additionally, the optical and electronic properties are applicable in biosensing, optical component coatings, and semiconductors. The wide interest has prompted extensive research in design and synthesis to facilitate property fine-tuning. This review summarizes synthetic methods for hafnium-based nanomaterials and applications in therapy, imaging, and biosensing with a mechanistic focus. A discussion and future perspective section highlights clinical progress and elaborates on current challenges. By focusing on factors impacting applicational effectiveness and examining limitations this review aims to support researchers and expedite clinical translation of future hafnium-based nanomedicine.

A simulation study on the radiosensitization properties of gold nanorods.

Objective. Gold nanorods (GNRs) have emerged as versatile nanoparticles with unique properties, holding promise in various modalities of cancer treatment through drug delivery and photothermal therapy. In the rapidly evolving field of nanoparticle radiosensitization (NPRS) for cancer therapy, this study assessed the potential of gold nanorods as radiosensitizing agents by quantifying the key features of NPRS, such as secondary electron emission and dose enhancement, using Monte Carlo simulations.Approach. Employing the TOPAS track structure code, we conducted a comprehensive evaluation of the radiosensitization behavior of spherical gold nanoparticles and gold nanorods. We systematically explored the impact of nanorod geometry (in particular size and aspect ratio) and orientation on secondary electron emission and deposited energy ratio, providing validated results against previously published simulations.Main results. Our findings demonstrate that gold nanorods exhibit comparable secondary electron emission to their spherical counterparts. Notably, nanorods with smaller surface-area-to-volume ratios (SA:V) and alignment with the incident photon beam proved to be more efficient radiosensitizing agents, showing superiority in emitted electron fluence. However, in the microscale, the deposited energy ratio (DER) was not markedly influenced by the SA:V of the nanorod. Additionally, our findings revealed that the geometry of gold nanoparticles has a more significant impact on the emission of M-shell Auger electrons (with energies below 3.5 keV) than on higher-energy electrons.Significance. This research investigated the radiosensitization properties of gold nanorods, positioning them as promising alternatives to the more conventionally studied spherical gold nanoparticles in the context of cancer research. With increasing interest in multimodal cancer therapy, our findings have the potential to contribute valuable insights into the perspective of gold nanorods as effective multipurpose agents for synergistic photothermal therapy and radiotherapy. Future directions may involve exploring alternative metallic nanorods as well as further optimizing the geometry and coating materials, opening new possibilities for more effective cancer treatments.

Nanoparticle-Mediated Radiotherapy: Unraveling Dose Enhancement and Apoptotic Responses in Cancer and Normal Cell Lines.

Cervical cancer remains a pressing global health concern, necessitating advanced therapeutic strategies. Radiotherapy, a fundamental treatment modality, has faced challenges such as targeted dose deposition and radiation exposure to healthy tissues, limiting optimal outcomes. To address these hurdles, nanomaterials, specifically gold nanoparticles (AuNPs), have emerged as a promising avenue. This study delves into the realm of cervical cancer radiotherapy through the meticulous exploration of AuNPs' impact. Utilizing ex vivo experiments involving cell lines, this research dissected intricate radiobiological interactions. Detailed scrutiny of cell survival curves, dose enhancement factors (DEFs), and apoptosis in both cancer and normal cervical cells revealed profound insights. The outcomes showcased the substantial enhancement of radiation responses in cancer cells following AuNP treatment, resulting in heightened cell death and apoptotic levels. Significantly, the most pronounced effects were observed 24 h post-irradiation, emphasizing the pivotal role of timing in AuNPs' efficacy. Importantly, AuNPs exhibited targeted precision, selectively impacting cancer cells while preserving normal cells. This study illuminates the potential of AuNPs as potent radiosensitizers in cervical cancer therapy, offering a tailored and efficient approach. Through meticulous ex vivo experimentation, this research expands our comprehension of the complex dynamics between AuNPs and cells, laying the foundation for their optimized clinical utilization.

Technical note: Evaluation of the dose enhancement effect for a novel transmission-type x-ray tube using the Monte Carlo method.

PURPOSE: Transmission-target x-ray tubes generate more x-rays than reflection thick-target x-ray tubes. A transmission x-ray tube combined with radiosensitizers has a better radiation enhancement effect. This study investigated the feasibility of using a transmission x-ray tube with radiosensitizers in clinical radiotherapy and its effect on radiation dose enhancement. METHODS: This study used MCNP6.2 to simulate the model of a transmission x-ray tube and Co-60 beam.   The radiation enhancement effect of radiosensitizers was examined with iodine-127 (I-127), radioiodinated iododeoxyuridine (IUdR), and gold nanoparticles (GNPs). RESULTS: The study results showed that the dose enhancement factor (DEF) of the transmission x-ray tube with GNPs was 10.27, which was higher than that of I-127 (6.46) and IUdR (3.08). The DEF of the Co-60 beam with GNPs, I-127, and IUdR was 1.23, 1.19, and 1.2, respectively. The Auger electron flux of the transmission x-ray tube with GNPs was 1.19E+05 particles/cm2 . CONCLUSIONS: This study found that a transmission x-ray tube with appropriate radiosensitizers could produce a high rate of Auger electrons to fulfill the radiation enhancement effect, and this procedure has the potential to become a radiotherapy modality.

Enhanced electron beam and X-ray beam therapy by applying nanoparticle heterojunctions: A Monte Carlo simulation.

Cancer has become one of the major diseases that seriously threaten human health. In order to improve the therapeutic gain ratio (TGF) of conventional X-ray and electron beams, we studied the dose enhancement effect and secondary electrons emission of Au-Fe nanoparticle heterostructures by Monte Carlo method. Under the irradiation of 6 MeV photon and 6 MeV electron beams, the Au-Fe mixture has a dose enhancement effect. For this reason, we explored the secondary electrons production that leads to dose enhancement. For 6 MeV electron beam irradiation, Au-Fe nanoparticle heterojunctions have an higher electrons emission than Au and Fe nanoparticles. When cubic, spherical and cylindrical heterogeneous structures are considered, the electron emission of the columnar Au-Fe nanoparticles is the highest, with a maximum value of 0.00024. For 6 MV X-ray beam irradiation, Au nanoparticle and Au-Fe nanoparticle heterojunction have similar electrons emission, while Fe nanoparticle has the lowest one. When cubic, spherical and cylindrical heterogeneous structures are considered, the electron emission of the columnar Au-Fe nanoparticles is the highest, with a maximum value of 0.000118. This study contributes to improve the tumor-killing effect of conventional X-ray radiotherapy treatment and has guiding significance for the research of new nanoparticles.

Measurement of dose enhancement factor for Xoft Axxent electronic brachytherapy device using nanoparticle-embedded alginate film and radiochromic film.

Aim: Inw nanoparticles-aided radiotherapy, the radiation sensitivity of tumor is increased with the infusion of nanoparticles in tumor. This therapeutic modality is capable of delivering enhanced dose to tumor, without exceeding the normal tissue tolerance dose. Further, the quantification of the enhanced dose using suitable dosimeter is important. The present study is aimed at measuring the dose enhancement factors (DEFs) using the combination of nanoparticles-embedded alginate (Alg) film and unlaminated Gafchromic EBT3 film. Materials and Methods: Gold nanoparticles (AuNPs)- and silver nanoparticles (AgNPs)-embedded Alg polymer films were synthesized and characterized using standard techniques. Further, a customized version of the Gafchromic EBT3 film, i.e., unlaminated EBT3 film, was specially fabricated. The DEFs were measured using Xoft Axxent electronic brachytherapy device. Results: The surface plasmon resonance (SPR) and particle size of AuNPs were found to be 550 and 15 ± 2 nm, respectively. In the case of AgNPs, the SPR and particle size were recorded as 400 and 13 ± 2 nm, respectively. The DEFs measured, using unlaminated EBT3 film, for Xoft Axxent electronic brachytherapy using AuNPs and AgNPs were 1.35 ± 0.02 and 1.20 ± 0.01, respectively. Conclusion: The increase in dose enhancement during nanoparticles-aided electronic brachytherapy can be attributed to dominance of photoelectric effect, due to the presence of low-energy X-rays. The investigation indicates that the Xoft Axxent electronic brachytherapy device is suitable for nanoparticles-aided brachytherapy.

Monte Carlo simulation of gold nanoparticles for X-ray enhancement application.

BACKGROUND: Gold nanoparticles (Au NPs) are regarded as potential agents that enhance the radiosensitivity of tumor cells for theranostic applications. To elucidate the biological mechanisms of radiation dose enhancement effects of Au NPs as well as DNA damage attributable to the inclusion of Au NPs, Monte Carlo (MC) simulations have been deployed in a number of studies. SCOPE OF REVIEW: This review paper concisely collates and reviews the information reported in the simulation research in terms of MC simulation of radiosensitization and dose enhancement effects caused by the inclusion of Au NPs in tumor cells, simulation mechanisms, benefits and limitations. MAJOR CONCLUSIONS: In this review, we first explore the recent advances in MC simulation on Au NPs radiosensitization. The MC methods, physical dose enhancement and enhanced chemical and biological effects is discussed, followed by some results regarding the prediction of dose enhancement. We then review Multi-scale MC simulations of Au NP-induced DNA damages for X-ray irradiation. Moreover, we explain and look at Multi-scale MC simulations of Au NP-induced DNA damages for X-ray irradiation. GENERAL SIGNIFICANCE: Using advanced chemical module-implemented MC simulations, there is a need to assess the radiation-induced chemical radicals that contribute to the dose-enhancing and biological effects of multiple Au NPs.

Radiotherapy reimagined: Integrating nanomedicines into radiotherapy clinical trials.

Radioenhancing nanoparticles (NPs) are being evaluated in ongoing clinical trials for various cancers including head and neck, lung, esophagus, pancreas, prostate, and soft tissue sarcoma. Supported by decades of preclinical investigation and recent randomized trial data establishing clinical activity, these agents are poised to influence future multimodality treatment paradigms involving radiotherapy. Although the physical interactions between NPs and ionizing radiation are well characterized, less is known about how these agents modify the tumor microenvironment, particularly regarding tumor immunogenicity. In this review, we describe the key multidisciplinary considerations related to radiation, surgery, immunology, and pathology for designing radioenhancing NP clinical trials. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Microdosimetric and radiobiological effects of gold nanoparticles at therapeutic radiation energies.

PURPOSE: The purpose of this study was to quantify the microscopic dose distribution surrounding gold nanoparticles (GNPs) irradiated at therapeutic energies and to measure the changes in cell survival in vitro caused by this dose enhancement. METHODS: The dose distributions from secondary electrons surrounding a single gold nanosphere and single gold nanocube of equal volume were both simulated using MCNP6. Dose enhancement factors (DEFs) in the 1 µm3 volume surrounding a GNP were calculated and compared between a nanosphere and nanocube and between 6 and 18 MV energies. This microscopic effect was explored further by experimentally measuring the cell survival of C-33a cervical cancer cells irradiated at 18 MV with varying doses of energy and concentrations of GNPs. Survival of cells receiving no irradiation, a 3 Gy dose, and a 6 Gy dose of 18 MV energy were determined for each concentration of GNPs. RESULTS: It was observed that the dose from electrons surrounding the gold nanocube surpasses that of a gold nanosphere up to a distance of 1.1 µm by 18.5% for the 18 MV energy spectrum and by 23.1% for the 6 MV spectrum. DEFs ranging from ∼2 to 8 were found, with the maximum DEF resulting from the case of the gold nanocube irradiated at 6 MV energy. Experimentally, for irradiation at 18 MV, incubating cells with 6 nM (0.10% gold by mass) GNPs produces an average 6.7% decrease in cell survival, and incubating cells with 9 nM (0.15% gold by mass) GNPs produces an average 14.6% decrease in cell survival, as compared to cells incubated and irradiated without GNPs. CONCLUSION: We have successfully demonstrated the potential radiation dose enhancing effects in vitro and microdosimetrically from gold nanoparticles.

Monte Carlo simulation of physical dose enhancement in core-shell magnetic gold nanoparticles with TOPAS.

The application of metal nanoparticles (MNPs) as sensitization materials is a common strategy that is used to study dose enhancement in radiotherapy. Recent in vitro tests have revealed that magnetic gold nanoparticles (NPs) can be used in cancer therapy under a magnetic field to enhance the synergistic efficiency in radiotherapy and photothermal therapy. However, magnetic gold NPs have rarely been studied as sensitization materials. In this study, we obtained further results of the sensitization properties of the magnetic gold NPs (Fe3O4@AuNPs) with or without magnetic field using the TOPAS-nBio Monte Carlo (MC) toolkit. We analyzed the properties of Fe3O4@AuNP in a single NP model and in a cell model under monoenergetic photons and brachytherapy, and we investigated whether the magnetic field contributes to the physical sensitization process. Our results revealed that the dose enhancement factor (DEF) of Fe3O4@AuNPs was lower than that of gold nanoparticles (AuNPs) in a single NP and in a cell irradiated by monoenergetic photons. But it's worth mentioning that under a magnetic field, the DEF of targeted Fe3O4@AuNPs in a cell model with a clinical brachytherapy source was 22.17% (cytoplasm) and 6.89% (nucleus) higher than those of AuNPs (50 mg/mL). The Fe3O4@AuNPs were proved as an effective sensitization materials when combined with the magnetic field in MC simulation for the first time, which contributes to the research on in vitro tests on radiosensitization as well as clinical research in future.