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Synchronous chemotherapy and radiotherapy, termed chemoradiation therapy, is now an important standard regime for synergistic cancer treatment. For such treatment, nanoparticles can serve as improved carriers of chemotherapeutics into tumors and as better radiosensitizers for localized radiotherapy. Herein, we designed a Schottky-type theranostic heterostructure, Bi2S3–Au, with deep level defects (DLDs) in Bi2S3 as a nano-radiosensitizer and CT imaging contrast agent which can generate reactive free radicals to initiate DNA damage within tumor cells under X-ray irradiation. Methotrexate (MTX) was conjugated onto the Bi2S3–Au nanoparticles as a chemotherapeutic agent showing enzymatic stimuli-responsive release behavior. The designed hybrid system also contained curcumin (CUR), which cannot only serve as a nutritional supplement for chemotherapy, but also can play an important role in the radioprotection of normal cells. Impressively, this combined one-dose chemoradiation therapeutic injection of co-drug loaded bimetallic multifunctional theranostic nanoparticles with a one-time clinical X-ray irradiation, completely eradicated tumors in mice after approximately 20 days after irradiation showing extremely effective anticancer efficacy which should be further studied for numerous anti-cancer applications., Graphical abstract Image 1, Highlights • Develop a novel theranostic hybrid heterostructure for synchronous chemoradiation therapy. • Combine all of the nano-radiosensitizer, drug carrier and CT imaging contrast agent in one system. • Achieve completely eradication tumors in mice by a single-dose injection and one-time irradiation.

Multifunctional nanoplatforms based on novel bimetallic nanoparticles have emerged as effective radiosensitizers owing to their potential capability in cancer cells radiosensitization. Implementation of chemotherapy along with radiotherapy, known as synchronous chemoradiotherapy, can augment the treatment efficacy. Herein, a tumor targeted nanoradiosensitizer with synchronous chemoradiotion properties, termed as CuFe

Low sensitivity of cancer stem cells toward regular cancer therapy strategies is an important issue in the field of cancer remedy. The concept of cancer stem cell elimination has been a topic of interest in the field of molecular medicine for a long time. At the current study, it was aimed to elevate the sensitivity of cancer stem-like cells toward radiotherapy by treating with Oct4-Sox2 complex decoy oligodeoxynucleotides (ODNs). After treating HT29 and HT29-ShE cells with Oct4-Sox2 complex decoy ODNs, and analyzing the cellular uptake and localization of decoys, treated cells and control groups were subjected to irradiation by fractionated 6MV X-ray with a final dose of 2 Gy. Thereafter, the influence of radiotherapy on ODNs treated groups and control group was investigated on cell viability, cell cycle, apoptosis, colonosphere formation and scratch assay. Cellular uptake and localization assays demonstrated that decoy ODNs can efficiently be transfected to the cells and reside in subcellular compartment, where they pose their action on gene regulation. Post radiotherapy analysis indicated statistical significance in decoy ODNs treated cells by means of lower cell viability, cell cycle arrest in G2/M phase, increased cellular apoptosis, and reduced cell motility. Also, formed colonospheres were smaller in size and fewer in numbers. Considering the role of Oct4, and Sox2 transcription factors in signaling pathways of preserving stemness and inducing reverse EMT, application of decoy strategy could increase the sensitivity of cancer cells toward irradiation, which has a potential to eliminate the cancerous cells from tumors and support cancer treatment.

The development of high-Z based metallic nanomaterials as radiosensitizers are limited due to having some challenges such as nonideal selectivity to the target tissue. In this work, we prepared X-r...

The goal of this work is to harness the advantages of a targeted hybrid nanostructure, BSA-coated Fe3O4 (F)-Au heterodimer, as a radiosensitizer and co-delivery vehicle of chemotherapeutic drugs for enhanced synergic cancer therapy and protection of healthy tissues. F-Au-BSA-MTX-CUR combines the abilities of enhanced X-ray radiation therapy (F-Au), long blood circulation time (BSA), tumor targeting (MTX), enhanced chemotherapy (MTX and CUR), and protection of normal cells against the harmful effects of radiation (CUR). In this work, we present the radioprotective and radiosensitizing effects of CUR on normal tissues and the tumor site, respectively. After technical evaluation, drug loading, drug release behavior, hemolysis assay, transfection efficacy, and cellular uptake studies with fluorescence microscopy, the biosafety and toxicity of the nanostructure was assessed in vitro and in vivo. Also, to confirm its power to improve synergistic chemoradiation therapy in mice, the antitumor effects of the designed treatment plan were assessed in a 4T1-tumor bearing mouse model. The in vivo antitumor effect evaluation interestingly reveals outstanding therapeutic power of the final formulation (F-Au-BSA-MTX-CUR) and further requirement of CUR as a radioprotective. This result importantly revealed the radioprotection effect of CUR. Co-delivery of the chemotherapeutic drugs MTX and CUR, combined with the radiosensitizing effect of the F-Au heterodimer and the radioprotective effect of CUR, showed promising prospects in cancer therapy.

High atomic number Z, nanoparticles are able to enhance the photoelectric and Compton effects under X-Ray irradiation resulting the increase of radiation therapy efficacy. To achieve enhanced radia...

Background: Cancer is defined as the uncontrolled growth of abnormal cells and the second most common cause of death across the world. More than half of new cancer cases are reported in developing countries, the prevalence of cancer is on the rise in these countries due to the lifestyle risk factors associated with cancer. It is predicted that cancer will become the main cause of death worldwide. The present study aimed to attain the epidemiologic data of cancer patients in Zanjan province, Iran. Methods: The data required for this descriptive study were obtained by reviewing the medical records of the patients during 2016-2018. Data analysis was performed by IBM SPSS version 25. Results: In total, 518 cancer cases were studied, (male-to-female ratio: 1.15). The mean age of the male patients was more than the females. The most common cancers were reported to be breast and brain cancer. The prevalence of cancer was higher in the residents of urban areas. Conclusion: Unlike the most of findings in this study, some of them were not in line with the studies conducted in the other provinces in Iran. Therefore, it is recommended that further investigations be conducted in this regard.

The development of highly integrated multifunctional nanomaterials with a superadditive therapeutic effect and good safety is an urgent but challenging task in cancer therapy research. The present study aims to design a nanoplatform that offers the opportunity to enhance antitumor activity while minimizing side effects. Given the Au-mediated X-ray radiation enhancement and the ability of Fe-based nanomaterials to create reactive oxygen species (ROS) and DNA damage, we anticipated that bimetallic Fe3O4-Au heterodimer would bring strong radiosensitizing capacity. Fe3O4-Au heterodimer surface was covered with bovine serum albumin (BSA) to achieve good surface functionality, stability and prolonged blood circulation. Folic acid (FA) moieties were added to the nanoformulation to increase tumor-homing, specificity and uptake. Finally, curcumin (CUR) was incorporated into the nanoparticle to function as a natural anticancer agent. The integration of all these components has yielded a single nanoplatform, Fe3O4-Au-BSA-FA-CUR, capable of successfully fulfilling the mission of superadditive cancer therapy to avoid the risks of organ removal surgery. The efficacy of the proposed nanoplatform was investigated in vitro and in vivo. High radiosensitizing ability, X-ray-induced ROS generation and DNA damage, and good biocompatibility were demonstrated through in vitro experiments. Also, the administration of Fe3O4-Au-BSA-FA-CUR with X-ray irradiation completely eradicated the tumor without any mortality and toxicity in healthy tissues in vivo. Our results highlight the potential of CUR-loaded Fe3O4-Au-BSA-FA heteronanostructure to enable synergistic localized radiochemotherapy and open up a new door to attractive possibilities that warrant further exploration.

X-ray usage in medical diagnosis could have hurtful effects for both patient and medical imaging wards’ personnel as a result of failure to follow radiation protection (RP) principles (shielding, distance and time) by radiographers. This cross-sectional descriptive–analytical study was carried out by valid and reliable online questionnaire, which was completed by 103 radiographers. Data were analyzed by using descriptive statistics (mean, standard deviation and frequency) and analytical statistics (Pearson’s correlation coefficient test, Student’s independent t-test and analysis of variance test) in the Statistical Package for Social Sciences version 20 (sig: P

Resistance to radiotherapy and chemotherapy has been a major problem of conventional cancer therapies, which consequently leads to cancer relapse and cancer-related death. It is known that cancer stem cells (CSCs) play a key role in therapy resistance and CSC-based targeted therapies have been considered as a powerful tool for cancer treatment. In the current study, we investigated the synergistic effects of suppressing signal transducer and activator of transcription (STAT3) function by decoy ODNs on X-irradiation (XI) and methotrexate (MTX) exposure as a combinational therapy in triple-negative breast cancer (TNBC) MDA-MB-231 cells. Lipofectamine 2000® was used as a transfecting agent and the cells treated with Scramble ODNs (SCR) and decoy ODNs were subjected to irradiation with 2 Gy at single/fractionated (XI group) doses, different concentration of MTX group, and X-irradiation-methotrexate (XI/MTX group). Synergistic effects of STAT3 SCR and decoy ODNs on cells were investigated by cell viability (MTT), cell cycle profile, apoptosis rate, migration, and invasion assays. Statistical analysis of obtained data showed that STAT3 decoy ODNs significantly decreased the cell viability, arrested the growth at G0/G1 phase, increased apoptosis rate, and reduced migrated and invaded cells through transwell membrane, in XI, MTX, and XI/MTX exposed groups. Since STAT3 is a master transcription factor in breast cancer cells stemness, aggressiveness, TNBC's heterogeneity, and therapy resistance; therefore, inhibition of this transcription factor by decoy ODNs could increase antitumor efficiencies of XI and MTX exposure strategies. Accordingly, this method could have the potential to increase the efficiency of combination therapies.

Objective: Ionizing radiation is a critical threat to biomolecules, especially DNA. Various combinatorial compounds have been studied to protect this biomolecule. Melatonin has been reported as a direct and indirect free radical scavenger, but in this study, we explored the effect of melatonin on assisting in DNA repair by expression of Cdkn1a and Rad50; both of these genes are involved in DNA repair signaling, induced by radiation in rat peripheral blood. Materials and Methods: Rats were irradiated with single whole-body linear accelerator X-ray radiation doses of 2 and 8 Gy with or without melatonin (100 mg/kg body weight) pretreatments. The rats were randomly divided into nine groups and given an intraperitoneal injection of melatonin or the same volume of vehicle alone 1 h before radiation. Blood samples were taken 8, 24, and 48 h postradiation to measure gene expression of Cdkn1a and Rad50 using quantitative reverse transcription polymerase chain reaction technique. Results: Melatonin pretreatment increased the expression of Cdkn1a and Rad50 in 8 and 24 h postradiations (2 and 8 Gy) (P < 0.05), and there was no significant difference in 48 h postradiation compared to the radiation-only and vehicle plus radiation (2 and 8 Gy) groups. Conclusions: Based on our results, pretreatment with melatonin (100 mg/kg) may ameliorates injurious effects of 2 and 8 Gy ionization radiation by increasing the expression level of Cdkn1a and Rad50 in rat peripheral blood and assist in DNA double-strand breaks repair, especially during the early postradiation.

This study aimed to evaluate the dose distribution of the Monte Carlo (MC) code and TiGRT treatment planning system (TPS) compared to experimental measurements. A thirteen-field Intensity-Modulated Radiation Therapy (IMRT) plan was created according to the RTOG H-0022 protocol. A film stack at distances of 3 mm and 1 mm was inserted into the phantom and irradiated. The dose distribution by this IMRT plan was also simulated using EGSnrc. The 3D dose distributions obtained from the TPS and MC calculations were compared against the film measurements (gold standard) using gamma index with conventional (3%-3 mm) and strict (2%-2 mm) criteria. The local gamma passing rate (GPR) for TiGRT-film and MC-film with the conventional criteria at the resolution of 3 mm was 89.36% and 97.94% respectively, and with a resolution of 1 mm, the agreement rate increased to 91.83% and 99.23%, respectively. With the strict criteria at the resolution of 1 mm, the percentage of agreements for TiGRT and MC was about 72.55% and 95.27%, respectively. From the research point of view, the 3D film dosimetry can be used as a valuable dosimetry tool for evaluating the 3D dose distribution in dose computing systems.

In this research, curcumin (CUR) conjugated albumin based nanoparticles (BSA-CUR) were designed for improvement and evaluation radioprotective effect of CUR. In this way, we have prepared BSA-CUR by covalently binding the CUR with BSA. Next, this synthesized prodrug was evaluated for physical and chemical properties by Fourier-transform infrared (FTIR), Dynamic light scattering (DLS), Transmission electron microscopy (TEM), Ultraviolet–visible (UV/Vis), and Differential scanning calorimetry (DSC) analysis. Furthermore, the chemical stability of designed prodrug was appraised. The result shows that the size of nanoparticles is 174.4 nm with a polydispersity index (PdI) of 0.191. The nanoparticles have a high loading capacity and show sustained release behavior. Loading of CUR to BSA not only could increase the chemical stability of CUR, but also could improve radioprotection efficacy of it's against X-Ray irradiation. The HHF-2 cells show 107% viability in the presence of BSA-CUR at a concentration of 50 µg/mL, whereas non-treated cells show 46% viability, under X-Ray irradiation. Also in vivo study results show that, four out of five mice have died when the mice irradiated by X-Ray and no received any treatment. Although, for a group that treated with BSA-CUR and also irradiated by X-Ray, median survival and survival rate was higher than CUR treated and control mice, and only two out of five mice have died. The result of this study proved that BSA-CUR can be used as a proficient vehicle for improving the potential radioprotective effect of CUR.

The application of nanoparticles (NPs) as radio-sensitizers and carriers has opened up a new horizon to overcome the limitations of chemo and radiotherapy. In this study, bovine serum albumin-coated Bi2S3 NPs (Bi2S3@BSA NPs) were synthesized and evaluated in terms of their ability to be used as a radio-sensitizer and carrier for methotrexate (MTX). Physicochemical properties of MTX conjugated Bi2S3@BSA NPs (Bi2S3@BSA-MTX NPs) were characterized by DLS, TEM, FTIR, UV/Vis, and XRD analyses. After the evaluation of cellular uptake and intracellular localization, the cytotoxicity of the combination of Bi2S3@BSA-MTX NPs and X-Ray radiation was analyzed against the SW480 cell line. The synthesized NPs exhibited spherical-like shapes and homogenous morphology, possessing a hydrodynamic diameter of 140.2 ± 5.71 nm (mean ± SD) and zeta potential of −25 mV. Also, the release study showed that the release of MTX is faster and higher in the presence of the proteinase K enzyme than the absence of the enzyme. The results of in-vitro chemo-radiation therapy indicated that the viability of treated cells with Bi2S3@BSA-MTX NPs is significantly lower than the cells treated with Bi2S3@BSA NPs. Furthermore, cells treated with Bi2S3@BSA-MTX NPs showed a lower degree of viability when combined with X-Ray radiation in comparison with the absence of irradiation, which confirmed the ability of the Bi2S3@BSA-MTX NPs as radio-sensitizer.

Objective: Approximately 70% of all cancer patients receive radiotherapy. Although radiotherapy is effective in killing cancer cells, it has adverse effects on normal cells as well. Melatonin (MLT) as a potent antioxidant and anti-inflammatory agent has been proposed to stimulate DNA repair capacity. We investigated the capability of MLT in the modification of radiation-induced DNA damage in rat peripheral blood cells. Materials and Methods: In this experimental study, male rats (n = 162) were divided into 27 groups (n = 6 in each group) including: irradiation only, vehicle only, vehicle with irradiation, 100 mg/kg MLT alone, 100 mg/kg MLT plus irradiation in 3 different time points, and control. Subsequently, they were irradiated with a single whole-body X-ray radiation dose of 2 and 8 Gy at a dose rate of 200 MU/min. Rats were given an intraperitoneal injection of MLT or the same volume of vehicle alone 1 h prior to irradiation. Blood samples were also taken 8, 24, and 48 h postirradiation, in order to measure the 8-oxoguanine glycosylase1 (Ogg1), Apex1, and Xrcc1 expression using quantitative real-time-polymerase chain reaction. Results: Exposing to the ionizing radiation resulted in downregulation of Ogg1, Apex1, and Xrcc1 gene expression. The most obvious suppression was observed in 8 h after exposure. Pretreatments with MLT were able to upregulate these genes when compared to the irradiation-only and vehicle plus irradiation groups (P < 0.05) in all time points. Conclusion: Our results suggested that MLT in mentioned dose may result in modulation of Ogg1, Apex1, and Xrcc1 gene expression in peripheral blood cells to reduce X-ray irradiation-induced DNA damage. Therefore, administration of MLT may increase the normal tissue tolerance to radiation through enhancing the cell DNA repair capacity. We believed that MLT could play a radiation toxicity reduction role in patients who have undergone radiation treatment as a part of cancer radiotherapy.

Understanding of cellular responses to ionizing radiation (IR) is essential for the development of predictive markers useful for assessing human exposure. Biological markers of exposure to IR in human populations are of great interest for assessing normal tissue injury in radiation oncology and for biodosimetry in nuclear incidents and accidental radiation exposures. Traditional radiation exposure biomarkers based on cytogenetic assays (biodosimetry), are time-consuming and do not provide results fast enough and requires highly trained personnel for scoring. Hence, the development of rapid biodosimetry methods is one of the highest priorities. Exposure of cells to IR activates multiple signal transduction pathways, which result in complex alterations in gene-expression. Real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR) has become the benchmark for the detection and quantification of RNA targets and is being utilized increasingly in monitoring the specific genes with more accurately and sensitively. This review evaluates the RT-qPCR as a biodosimetry method and we investigated the papers from 2000 up to now, which identified the genes-expression related the DNA repair, cell cycle checkpoint, and apoptosis induced by ionization radiation in peripheral blood and determined as biodosimeters. In conclusion, it could be say that RT-qPCR technique for determining the specific genes as biodosimeters could be a fully quantitative reliable and sensitive method. Furthermore, the results of the current review will help the researchers to recognize the most expressed genes induced by ionization radiation.

Context: In radiation treatments, estimation of the dose distribution in the target volume is one of the main components of the treatment planning procedure. To estimate the dose distribution, the information of electron densities is necessary. The standard curves determined by computed tomography (CT) scanner that may be different from that of other oncology centers. In this study, the changes of dose calculation due to the different calibration curves (HU-ρel ) were investigated. Materials and Methods: Dose values were calculated based on the standard calibration curve that was predefined for the treatment planning system (TPS). The calibration curve was also extracted from the CT images of the phantom, and dose values were calculated based on this curve. The percentage errors of the calculated values were determined. Statistical Analysis Used: The statistical analyses of the mean differences were performed using the Wilcoxon rank-sum test for both of the calibration curves. Results and Discussion: The results show no significant difference for both of the measured and standard calibration curves (HU-ρel ) in 6, 15, and 18 MeV energies. In Wilcoxon ranked sum nonparametric test for independent samples with P < 0.05, the equality of monitor units for both of the curves to transfer 200 cGy doses to reference points was resulted. The percentage errors of the calculated values were lower than 2% and 1.5% in 6 and 15 MeV, respectively. Conclusion: From the results, it could be concluded that the standard calibration curve could be used in TPS dose calculation accurately.

Aims: The objective of this study is to evaluate the accuracy of a treatment planning system (TPS) for calculating the dose distribution parameters in conformal fields (CF). Dosimetric parameters of CF's were compared between measurement, Monte Carlo simulation (MCNP4C) and TPS calculation. Materials and Methods: Field analyzer water phantom was used for obtaining percentage depth dose (PDD) curves and beam profiles (BP) of different conformal fields. MCNP4C was used to model conformal fields dose specification factors and head of linear accelerator varian model 2100C/D. Results: Results showed that the distance to agreement (DTA) and dose difference (DD) of our findings were well within the acceptance criteria of 3 mm and 3%, respectively. Conclusions: According to this study it can be revealed that TPS using equivalent tissue air ratio calculation method is still convenient for dose prediction in non small conformal fields normally used in prostate radiotherapy. It was also showed that, since there is a close correlation with Monte Carlo simulation, measurements and TPS, Monte Carlo can be further confirmed for implementation and calculation dose distribution in non standard and complex conformal irradiation field for treatment planning systems.

Background: After radiation therapy (RT), some health hazards including DNA damages may occur where melatonin can play a protective role due to free radical generation. On the other hand, serious accidental overexposures may occur during RT due to nuclear accidents which necessitate the need for study on exposure to high-dose radiations during treatments. Objective: The aim of this study was to study the expression level of two genes in non-homologous end joining (NHEJ) pathways named Xrcc4 and Xrcc6 (Ku70) in order to examine the effect of melatonin on repair of DNA double-strand breaks (BSBs) caused by 8Gy ionizing radiation. Methods: One hundred eight male Wistar rats were irradiated with a whole body gamma radiation dose of 8Gy with or without melatonin pretreatments. They were divided into six different groups of control, 100 mg/kg melatonin alone, 8Gy irradiation alone, vehicle alone, vehicle plus 8Gy irradiation and 100 mg/kg melatonin plus 8Gy irradiation. Peripheral blood samples were collected at 8, 24 and 48 h after irradiation. Ku70 and Xrcc4 gene expression were evaluated by real-time quantitative polymerase chain reaction (qPCR) technique and analyzed by one-way ANOVA test. Results: Expression of Ku70 and Xrcc4 genes normalized against Hprt gene showed significant difference in melatonin plus irradiation group at 8h compared to the control group (p

Funding Information: This work supported by the “ Iran National Science Foundation : INSF-98024375 ”, Iran's National Elites Foundation , and the “ University of Zanjan ”. We gratefully acknowledge the Zanjan University of Medical Science support. JC acknowledges financial support from the European Research Council - ERC Starting Grant 848325 . Y.N. Ertas acknowledges funding support from the 2232 International Fellowship for Outstanding Researchers Program of TÜBİTAK (Project No: 118C346 ). MB acknowledges the financial support of the International Atomic Energy Agency (IAEA) under coordinated research project F22070 (IAEA Research Contract No: 23192 ). Funding Information: This work supported by the “Iran National Science Foundation: INSF-98024375”, Iran's National Elites Foundation, and the “University of Zanjan”. We gratefully acknowledge the Zanjan University of Medical Science support. JC acknowledges financial support from the European Research Council - ERC Starting Grant 848325. Y.N. Ertas acknowledges funding support from the 2232 International Fellowship for Outstanding Researchers Program of TÜBİTAK (Project No: 118C346). MB acknowledges the financial support of the International Atomic Energy Agency (IAEA) under coordinated research project F22070 (IAEA Research Contract No: 23192). Publisher Copyright: © 2022 Janus heterostructures based on bimetallic nanoparticles have emerged as effective radiosensitizers owing to their radiosensitization capabilities in cancer cells. In this context, this study aims at developing a novel bimetallic nanoradiosensitizer, Bi2S3-Fe3O4, to enhance tumor accumulation and promote radiation-induced DNA damage while reducing adverse effects. Due to the presence of both iron oxide and bismuth sulfide metallic nanoparticles in these newly developed nanoparticle, strong radiosensitizing capacity is anticipated through the generation of reactive oxygen species (ROS) to induce DNA damage under X-Ray irradiation. To improve blood circulation time, biocompatibility, colloidal stability, and tuning surface functionalization, the surface of Bi2S3-Fe3O4 bimetallic nanoparticles was coated with bovine serum albumin (BSA). Moreover, to achieve higher cellular uptake and efficient tumor site specificity, folic acid (FA) as a targeting moiety was conjugated onto the bimetallic nanoparticles, termed Bi2S3@BSA-Fe3O4-FA. Biocompatibility, safety, radiation-induced DNA damage by ROS activation and generation, and radiosensitizing ability were confirmed via in vitro and in vivo assays. The administration of Bi2S3@BSA-Fe3O4-FA in 4T1 breast cancer murine model upon X-ray radiation revealed highly effective tumor eradication without causing any mortality or severe toxicity in healthy tissues. These findings offer compelling evidence for the potential capability of Bi2S3@BSA-Fe3O4-FA as an ideal nanoparticle for radiation-induced cancer therapy and open interesting avenues of future research in this area. publishersversion published