Enhancement of the effect of novel targeted 5-aminolevulinic acid conjugated bismuth oxide nanoparticles-based photodynamic therapy by simultaneous radiotherapy on KB cells.

BACKGROUND: Selective accumulation of photosensitizers into cancerous cells is one of the most important factors affecting photodynamic therapy (PDT) efficacy. 5-aminolevulinic acid (5-ALA) is the precursor of a strong photosensitizer, protoporphyrin-IX; but it has poor permeability into the cells. Folate receptors are overexpressed on the surface of many tumor cells. In the present study, folic acid (FA) and 5-ALA conjugated bismuth oxide nanoparticles were synthesized; and used in PDT, radiotherapy (RT), and concurrent PDT & RT against nasopharyngeal carcinoma (KB cell line). METHODS: The KB cells were incubated with the synthesized nanoparticles (NPs) for 2 h; then illuminated using a custom-made LED lamp at the light dose of 26 J/cm2. Irradiation of the cells was carried out using X-ray 6 MV (2 Gy); and synergistic effect of the simultaneous RT and PDT treatments was evaluated using fractional product values. Efficacy of the treatments was determined using MTT and Caspase-3 enzyme activity assays. RESULTS: Targeting of folic acid receptors enables the selective endocytosis of the conjugated NPs. RT results in the presence of Bi2O3 NPs showed a significant radiosensitizer potential of these NPs. Fractional product values of 1.49±0.05, 1.36±0.06, and 1.05±0.06 obtained in the presence of FA-5-ALA conjugated NPs, 5-ALA conjugated NPs, and in the absence of the NPs, respectively. Therefore, simultaneous RT and PDT in the presence of these conjugated NPs is superior to RT in the presence of the NPs. CONCLUSION: Simultaneous PDT and RT in the presence of FA-5-ALA conjugated bismuth oxide NPs can be introduced as a promising therapeutic approach in controlling KB cancer cells.

Estimation of cancer risks due to chest radiotherapy treatment planning computed tomography (CT) simulations.

The objective of our study was to determine organ doses to estimate the lifetime attributable risk (LAR) of cancer incidence related to chest tomography simulations for Radiotherapy Treatment Planning (RTTP) using patient-specific information. Patient data were used to calculate organ doses and effective dose. The effective dose (E) was calculated by two methods. First, to calculate effective dose in a standard phantom, the collected dosimetric parameters were used with the ImPACT CT Patient Dosimetry Calculator and E was calculated by applying related correction factors. Second, using the scanner-derived Dose Length Product, LARs were computed using the US National Academy of Sciences (BEIR VII) model for age- and sex-specific risks at each exposure. DLP, CTDIvol, and scan length were 507 ± 143 mGy.cm, 11 ± 4 mGy, and 47 ± 7 cm, respectively. The effective dose was 10 ± 3 mSv using ImPACT patient dosimetry calculator software and 9 ± 2 mSv using the scanner-derived Dose Length Product. The LAR of cancer incidence for all cancers, all solid cancers and leukemia were 65 ± 29, 62 ± 27, 7 ± 2 cases per 100,000 individuals, respectively. Radiation exposure from the usage of CT for radiotherapy treatment planning (RTTP) causes non-negligible increases in lifetime attributable risk. The results of this study can be used as a guide by physicians to implement strategies based on the As Low As Reasonably Achievable (ALARA) principle that lead to a reduction dose without sacrificing diagnostic information.

Investigation of electrocardiography and echocardiography changes after adjuvant radiation therapy of left-sided breast cancer.

INTRODUCTION: The primary objective of radiation therapy (RT) is to deliver lethal radiation doses to abnormal cancer cells so that healthy cells are exposed to minimal radiation. In the present study, changes in electrocardiography (ECG) and echocardiography(ECHO) following adjuvant RT were investigated in patients with left-sided breast cancer. MATERIALS AND METHODS: 30 patients with left-sided breast cancer who had previously undergone breast-conserving surgery or mastectomy underwent RT after completing chemotherapy from February 2019 to January 2020. ECG and ECHO tests were performed before RT, immediately following RT, and three months after RT. Dose-volume parameters of the heart and its substructures as an organ at risk were analyzed. RESULTS: The mean heart dose (±SD) for all patients was 7.51 ± 2.42 Gy. T-wave inversion was observed 3 months after RT in 47% of patients. T-wave decline was associated with mean heart radiation dose (ß = 0.605, p-value = 0.005). The present study showed that the left ventricular volume receiving the 5 Gy (LV-V5) parameter was associated with a reduction in ST segment duration (p-value = 0.027) as well as with an increase in left ventricular systolic diameter (LVESD, mm) (P-value = 0.027). CONCLUSION: RT-induced ECG and ECHO changes are frequent in patients with left breast cancer. LVEF and Twave abnormalities were observed after RT in our patients. ECG and ECHO modalities can be used to monitor the cardiac function after RT in patients with left-sided breast cancer.

Effective Connectivity within the Papez Circuit in the Multiple Sclerosis Patients: A Comparative Study Using Resting-State fMRI.

Background: Multiple sclerosis (MS) disease causes structural and functional damage to brain. Structural imaging of the MS-induced damage cannot adequately describe the functional impairment of the brain in MS patients. Therefore, it seems that advanced functional imaging analysis such as functional magnetic resonance imaging (fMRI) data is needed for better management of this disease. Objective: The aim of present study was to evaluate the effective connectivity within the Papez circuit in MS patients using resting-state fMRI. Material and Methods: In this cross-sectional analytical study, 22 healthy individuals and 24 patients with MS underwent resting-state fMRI. After pre-processing of the obtained data, the time series of Cingulate gyrus (CG), Para hippocampus gyrus (PHG), anterior thalamic nuclei (ATN), Mammillary body (MB), and Hippocampus (HPC) were extracted as the main Papez circuit components. The obtained time series were statistically analyzed as an input of the dynamic causal model in order to evaluate the effective connectivity in the Papez circuit. Results: The power of effective connectivity between each pair of tested nodes in Papez circuit was significantly lower in MS patients than healthy subjects. Also, the effective connectivity level of MS patients in direction of HPC→ATN was higher in men than women. In addition, effective self-connection in CG→CG and MB→MB regions in healthy subjects were higher in women than them in men. Conclusion: The present study reveals significant difference in effective connectivity of the Papez nodes in MS patients than control group, which can be exploited to diagnosis and predict or evaluate the treatment response of these patients.

Simultaneous effect of gamma and Wi-Fi radiation on gamma-H2Ax expression in peripheral blood of rat: A radio-protection note.

INTRODUCTION: Nuclear medicine patients are isolated in a room after the injection of a radiopharmaceutical. They may be active Wi-Fi option of its smartphone mobile or other environmental radiofrequency waves. The hypothesis of this study was the evaluation of increased biological effects of the simultaneous exposure to gamma-ray and the Wi-Fi waves by measuring the level of the increased double strand-breaks DNA in peripheral blood lymphocyte in the rat. MATERIALS AND METHODS: Fifty male Wistar rats were exposed for 2, 24, and 72 h only by Wi-Fi, 99m Tc, and simultaneously by Wi-Fi and 99m Tc. The power density levels of Wi-Fi emitter at 15 cm was 4.2nW/ c m 2 . An activity of 100 µCi of 99m Tc was injected intraperitoneally. Blood samples were taken by cardiac puncture following general anesthesia. Mononuclear cells are extraction by Ficoll-Hypaque density gradient centrifugation. The number of gamma-H2AX foci per nucleus was counted by flow cytometry. The statistical differences between experimental groups at 2, 24, and 72 h were determined with a repeated measure's analysis of variance. The significant difference between groups at the same time was analyzed with the Kruskal-Wallis Test. RESULTS: The manner of gamma-H2AX expression was not the same for three groups in time. The number of gamma-H2AX foci between the three groups was a significant difference after 72 h. CONCLUSION: Simultaneous Wi-Fi and gamma-ray exposures can increase the number of double-strand break DNA in peripheral blood lymphocytes to exposure of gamma-ray to 72 h after technetium injection in the rat.

Effective connectivity within the corticothalamic circuit in the neuromyelitis optica patients: A comparative study using resting-state fMRI.

Neuromyelitis Optica, which is known as NMO, is a demyelination syndrome and inflammatory condition of the central nervous system that affects the optic nerves. Since structural imaging approaches cannot adequately describe the brain disorders in patients with NMO, functional magnetic resonance imaging (fMRI) can be used. Resting-state fMRI was performed on 25 healthy subjects and 26 NMO patients. After preprocessing the data, the time series belonging to the regions of the middle frontal gyrus (MFG), inferior frontal gyrus (IFG), precuneus (PRE), thalamus (THA), and middle temporal gyrus (MTG) were extracted as components of the corticothalamic circuit. The obtained time series were statistically analyzed as the input of dynamic causal modeling (DCM) in order to evaluate the effective connectivity within the corticothalamic circuit. The statistical analyses showed that the mean of effective connectivity power was significantly higher in the healthy subjects than in the NMO patients. For the healthy subjects, there was no significant difference in effective connectivity power between the two groups of males and females at the significance level of 0.05. In the NMO patients, there was a significant difference between the effective connectivity levels of the male and female groups only for IFG â†’ MFG, in which it was greater in males than in females. The results of our studies showed that resting-state fMRI could exhibit the difference between healthy and NMO subjects.

EYE LENS DOSE OPTIMIZATION THROUGH GANTRY TILTING IN BRAIN CT SCAN: THE POTENTIAL EFFECT OF THE RADIOLOGICAL TECHNOLOGISTS' TRAINING.

This study was designed to evaluate the effect of the radiological technologists' training on optimising the eye lens dose in brain computed tomography (CT) examinations. The lens dose of 50 adult patients was measured using thermoluminescent dosimeters before and after technologists' training. Dose values of lenses, dose length product (DLP), volumetric CT dose index (CTDIvol) as well as image quality in terms of quantitative (contrast to noise ratio and signal to noise ratio) and subjective (artefact) parameters were compared before and after training. Lens dose values were 31.57 ± 9.84 mGy and 5.36 ± 1.53 mGy before and after training, respectively, which was reduced by ~83% (p < 0.05). The values of DLP, CTDIvol and image quality parameters were not significantly different (p > 0.05) and all images were diagnostically acceptable. Excluding the orbits from the scanning range is an efficient approach to optimize the lens dose; the training of the technologists has also a pivotal role in dose reducing.

Analysis of Glioblastoma Multiforme Tumor Metabolites Using Multivoxel Magnetic Resonance Spectroscopy.

BACKGROUND: Glioblastoma Multiforme (GBM) is the most common and deadly type of primary brain tumor in adults. Magnetic Resonance Spectroscopy (MRS) is a noninvasive imaging technique used to study metabolic changes in the brain tumors. Some metabolites such as Phosphocholine, Creatine, NAA/Cr, and Pcho/Cr have been proven to show a diagnostic role in GBM. The present study was conducted to analyze important metabolites using MRS multivoxel in GBM tumor. METHODS: In this study, information was collected from 8 individuals diagnosed with GBM using Siemens multivoxel MRS with a magnetic field strength of 3 T. Data were obtained by Point-Resolved Spectroscopy (PRESS) protocol with TE=135 ms and TR=1570 ms. NAA, Pcho, Cr, Ala, Gln, Gly, Glu, Lac, NAAG, and Tau metabolites were extracted and evaluated statistically. RESULTS: Given total number of normal voxels and total number of all voxels, levels of Cr, Glu, NAA, NAAG, and Gly/Tau ratio in healthy voxels were significantly higher than tumoral voxels (p=0.005, p=0.03, p<0.001, p<0.001 and p=0.041, respectively). In contrast, levels of Gly, Gln, Tau, Lac/Cr, Pcho/Cr, Pcho/NAA, Lac/NAA, and Gln/Glu ratios in tumoral voxels were significantly more than healthy voxels (p=0.001, p= 0.037, p<0.001, p=0.010, p<0.001, p<0.001, and p=0.024, respectively). However, levels of Lac and Pcho had no significant difference in the two types of voxels. CONCLUSION: In summary, compared to patients with glioblastoma with 1H-MRS, the Pcho/Cr and Pcho/NAA ratios, and NAAG are the most important parameters to differentiate between tumoral and normal voxels.

Monte Carlo simulation and performance assessment of GE Discovery 690 VCT positron emission tomography/computed tomography scanner.

The aim of this study is to simulate GE Discovery 690 VCT positron emission tomography/computed tomography (PET/CT) scanner using Geant4 Application for Tomographic Emission (GATE) simulation package (version 8). Then, we assess the performance of scanner by comparing measured and simulated parameter results. Detection system and geometry of PET scanner that consists of 13,824 LYSO crystals designed in 256 blocks and 24 ring detectors were modeled. In order to achieve a precise model, we verified scanner model. Validation was based on a comparison between simulation data and experimental results obtained with this scanner in the same situation. Parameters used for validation were sensitivity, spatial resolution, and contrast. Image quality assessment was done based on comparing the contrast recovery coefficient (CRC) of simulated and measured images. The findings demonstrate that the mean difference between simulated and measured sensitivity is <7%. The simulated spatial resolution agreed to within <5.5% of the measured values. Contrast results had a slight divergence within the range below 4%. The image quality validation study demonstrated an acceptable agreement in CRC for 8:1 and 2:1 source-to-background activity ratio. Validated performance parameters showed good agreement between experimental data and simulated results and demonstrated that GATE is a valid simulation tool for simulating this scanner model. The simulated model of this scanner can be used for future studies regarding optimization of image reconstruction algorithms and emission acquisition protocols.

LOCAL DRLS FOR PAEDIATRIC CT EXAMINATIONS BASED ON SIZE-SPECIFIC DOSE ESTIMATES IN KERMANSHAH, IRAN.

Due to the radiosensitivity of paediatric patients to X-ray, it is necessary to survey the paediatric DRLs using size-specific dose estimates (SSDE). In the present study, we determined the local diagnostic reference levels (DRLs) for paediatric chest, head and abdomen-pelvis CT examinations and their Surview scans in Kermanshah city, Iran. For ≤1 year, 1-5 years, 5-10 years and 10-15 years the DRLs (mGy) based on SSDE were determined N/A, 6.00, 6.25, 8.27 for abdomen-pelvis, and 8.74, 7.45, 11.15, 10.45 for chest and 19.05, 18.33, 18.22, 20.14 for head examinations, respectively. The differences between body size and default phantom defined in CT scanners are significant and should be considered when determining the DRLs. Based on our findings, use of CTDIv and SSDE parameters for determining DRLs leads to significant different results in children; thus SSDE is suggested as a more accurate index than CTDIV for establishing DRLs in paediatric CT examinations.

Application of dextran-coated iron oxide nanoparticles in enhancing the radiosensitivity of cancerous cells in radiotherapy with high-energy electron beams.

PURPOSE: Nowadays, cancer is one of the most important causes of morbidity and mortality in the world. The ideal aim of radiotherapy is delivering a lethal radiation dose to tumor cells while minimizing radiation exposure to healthy tissues around the tumor. One way to increase the dose in the tumor cells is the use of high-atomic number nanoparticles as radiosensitizer agents in these cells. The aim of this in vitro study was investigating the radiosensitization enhancement potential of the dextran-coated iron oxide nanoparticles (IONPs) on HeLa and MCF-7 cell lines in irradiations with high-energy electron beams. MATERIALS AND METHODS: In this in vitro study, the cytotoxicity level of dextran-coated IONPs at different concentrations (10, 40, and 80 µg/ml) was assessed on HeLa and MCF-7 cell lines. To evaluate the radiosensitivity effect, the nanoparticles were incubated with the cells at different concentrations for 24 h and afterward irradiated with different doses (0, 2, 4, 6, and 8 Gy) of 6 and 12 MeV electron beams. The cells survival fractions were obtained by the methylthiazoletetrazolium assay. RESULTS: Toxicity results of the nanoparticles at 10 and 40 µg/ml concentrations showed no significant cytotoxicity effect. The cells survival rates in groups receiving radiation in the absence and presence of IONPs showed a significant difference. The radiosensitivity enhancement induced by the nanoparticles in MCF-7 cell line was more than it in HeLa cell line. The average of radiosensitization enhancement factor at 10, 40, and 80 µg/ml concentrations and under 6 MeV irradiations obtained as 1.13, 1.19, 1.25, and 1.26, 1.28, 1.29 for HeLa, and MCF-7 cells, respectively. When 12 MeV electron beams were carried out, the values of 1.17, 1.26, 1.32, and 1.29, 1.32, 1.35 were obtained for the cells at the mentioned concentrations, respectively. Furthermore, the significant differences were observed in radiosensitization enhancement between 6 and 12 MeV electron beams irradiations. CONCLUSION: Use of dextran-coated IONPs can increase radiosensitivity and consequently at a given absorbed dose more cell killing will occur in cancerous cells. In other words, these nanoparticles can improve the efficiency of electron therapy.

Evaluating the photodynamic therapy efficacy using 5-aminolevulinic acid and folic acid-conjugated bismuth oxide nanoparticles on human nasopharyngeal carcinoma cell line.

Selective accumulation of photosensitizers (PSs) into cancerous cells is one of the most important factors affecting photodynamic therapy (PDT) efficacy. 5-Aminolevulinic acid (5-ALA) is precursor of a strong PS, protoporphyrin-IX (Pp-IX); but it has poor permeability in lipophilic membrane of the cells due to its hydrophilic property. Therefore, establishment of an improved delivery strategy could highly affect on treatment outcome. Moreover, folate receptors (FRs) are overexpressed on the surface of many tumor cells. In the present work, targeting ligand folic acid (FA) and 5-ALA conjugated bismuth oxide nanoparticles (FA-5ALA-Bi2O3 NPs) were synthesized; and used in PDT against human nasopharyngeal carcinoma cells (KB cell line). The KB cells incubated with the synthesized NPs for 2 h; then illuminated using a custom-made red light LED lamp at the light dose of 26 J/cm2. MTT and caspase-3 activity assays were performed to evaluate the efficacy of treatment. Results showed that FR targeting ligand enables selective endocytosis of FA-5-ALA-conjugated NPs into KB cells. Improved internalization of 5-ALA into cells decreased the cell viability to about 50%, 65%, and 85% in the groups receiving FA-5ALA-Bi2O3 NPs, 5ALA-Bi2O3 NPs, free 5-ALA and subsequent PDT, respectively. Therefore, FA-5ALA-Bi2O3 NPs can significantly increase the cell killing effect of PDT.

In vitro outlook of gold nanoparticles in photo-thermal therapy: a literature review.

Hyperthermia is an anti-cancer treatment in which the temperature of the malignant tumor is increased more than other adjacent normal tissues. Microwave, ultrasound, laser, and radiofrequency sources have been used for hyperthermia of cancerous tissues. In the past decade, near-infrared (NIR) laser for cancer therapy, known as photo-thermal therapy (PTT), was expanded in which the photo-sensitizer agent converts the light photon energy to heat. The heat following PTT can destroy cancer cells. There are some photo-sensitizer agents which have been used for PTT; however, owing to recent advances in nanotechnology, noble metal nanoparticles like gold (Au) nanoparticles (GNPs) have been used successfully in PTT. GNPs have some desirable specifications, including simple and controlled synthesis, small size, high level of biocompatibility, and surface plasmon resonance (SPR). The SPR effect of the GNPs increases the radiative properties like absorption and scattering; therefore, they can be used in PTT. In this article, we reviewed recent in vitro studies of PTT using GNPs in literature. At first, we focus on the physical properties of GNPs, their interaction with infrared radiation, and physical parameters governing the interaction of infrared radiation with the GNPs. Then, we review the passive and active targeting of GNPs using the different coating to induce the thermal damage in cancer cells using low-level laser PPT. The GNPs' cellular internalization into cancer cells is a challenge which is consequently considered. In this review, we also summarize the results of synergistic cancer therapy studies on the combination of radiation therapy as a routine cancer treatment and PTT: in which significant improvement occurs in treatment efficacy.

Investigating the Cytotoxicity of Folate-Conjugated Bismuth Oxide Nanoparticles on KB and A549 Cell Lines.

Purpose: Lately, bismuth-based nanomaterials have been widely utilized in medical researches such as imaging, drug delivery and radio-sensitization. Despite their advantages, bismuth-based compounds have shown toxic effects in humans. There are few studies on cytotoxicity effects of bismuth oxide (Bi2O3) nanoparticles (NPs) in-vitro. In this study, we aimed to investigate cytotoxicity of bare and also folate and 5-aminolevulinic acid (5-ALA)-conjugated Bi2O3 NPs on nasopharyngeal carcinoma (KB) and lung cancer (A549) cell lines. Methods: Bi2O3 NPs were synthesized and conjugated with folate and 5-ALA. KB and A549 cells were cultured and incubated with 10, 20, 50 and 100 µg/ml concentrations of bare and folate-5-ALA-conjugated NPs. The survival rates were obtained after 2 and 24 hours incubation of the cells with NPs using MTT assay. Also, apoptosis and ROS generation induced by the NPs in the treated cells were obtained using Caspases-3 activity assay and flow cytometry analysis, respectively. Results: Bi2O3 NPs were successfully synthesized with average size of 19.2 ± 6.5 nm, then conjugated with 5-ALA and folate. Either naked or folate-conjugated NPs were easily taken up by the cells in a concentration-dependent manner and showed cytotoxic effects. The significant cell death was noted at the concentrations more than 50 µg/ml for both compounds. Conclusion: Results indicated low cytotoxicity of the prepared NPs at lower incubation periods, which is very important for their further applications. However, 24 hours incubation of the cells with both forms of NPs caused more cell killing and the cytotoxicity increased with increasing concentrations of the NPs.

The Correction of Focal Point Displacement Caused by the Refraction of the Beams in High-Intensity Focused Ultrasound.

Nowadays, high-intensity focused ultrasound (HIFU) as nonionizing radiation is used for cancer treatment. Basically, the function of HIFU is similar to conventional ultrasound. Ultrasound beams are perverted when crossing the border of different environments. This decreases the beam's focus within the tumor and may induce damage to the normal tissues. In this study, we aim to develop appropriate algorithms for correcting the focal point displacement duced by the beam's refraction. First, the level of displacement due to difference in two specific tissues was calculated for one element of the transducer and, then, it extended to all of the elements. Finally, a new focal point was calculated, which is considered as a desired focal point of the transducer in which the maximum temperature occurs. Designed algorithms were implemented in MATLAB software. A HIFU simulator (by the Food and Drug Administration of US) was used to simulate HIFU therapy. The proposed algorithm was tested on four models with two layers of tissue. Results illustrated the use of proposed algorithm results for 78% correction in the focal point displacement. In addition, it was noted that a part of this displacement was caused by the absorption of the beam in the tissues. The proposed algorithm can significantly correct the focal point displacement in HIFU therapy and consequently prevent damage to the normal tissues.

CT images and radiotherapy treatment planning of patients with breast cancer: A dataset.

The data presented here were originally collected for the research project "CT-Scan processing and analysis in patient with breast cancer after radiotherapy". Also, it reported in our study "Prediction of Lung Tissue Damage by Evaluating Clinical and Dosimetric Parameters in Breast Cancer Patients" (Hasanabdali et al., 2016) [1]. This article describes and directly links to 52 subjects referred to Mahdieh Oncology and Radiotherapy Center from February to August 2015. Treatment planning was done for delivering 50 Gy dose to PTV in 25 fractions. the lungs and heart objects were extracted from CT images along with compliance Dose plan. Dose-volume histogram (DVH) and Dose-mass histogram (DMH) extracted using CT images and dose plan matrix. Moreover, the complete clinical and dosimetric specifications of subjects is attached.

Radiation dose rate affects the radiosensitization of MCF-7 and HeLa cell lines to X-rays induced by dextran-coated iron oxide nanoparticles.

BACKGROUND AND PURPOSE: The aim of radiotherapy is to deliver lethal damage to cancerous tissue while preserving adjacent normal tissues. Radiation absorbed dose of the tumoral cells can increase when high atomic nanoparticles are present in them during irradiation. Also, the dose rate is an important aspect in radiation effects that determines the biological results of a given dose. This in vitro study investigated the dose-rate effect on the induced radiosensitivity by dextran-coated iron oxide in cancer cells. MATERIALS AND METHODS: HeLa and MCF-7 cells were cultured in vitro and incubated with different concentrations of dextran-coated iron oxide nanoparticles. They were then irradiated with 6 MV photons at dose rates of 43, 185 and 370 cGy/min. The MTT test was used to obtain the cells' survival after 48 h of irradiations. RESULTS: Incubating the cells with the nanoparticles at concentrations of 10, 40 and 80 µg/ml showed no significant cytotoxicity effect. Dextran-coated iron oxide nanoparticles showed more radiosensitivity effect by increasing the dose rate and nanoparticles concentration. Radiosensitization enhancement factors of MCF-7 and HeLa cells at a dose-rate of 370 cGy/min and nanoparticles' concentration of 80 µg/ml were 1.21 ± 0.06 and 1.19 ± 0.04, respectively. CONCLUSION: Increasing the dose rate of 6 MV photons irradiation in MCF-7 and HeLa cells increases the radiosensitization induced by the dextran-coated iron nanoparticles in these cells.

Enhancement of radiosensitivity of melanoma cells by pegylated gold nanoparticles under irradiation of megavoltage electrons.

PURPOSE: Gold nanoparticles (GNP) have significant potential as radiosensitizer agents due to their distinctive properties. Several studies have shown that the surface modification of nanoparticles with methyl polyethylene glycol (mPEG) can increase their biocompatibility. However, the present study investigated the radiosensitization effects of mPEG-coated GNP (mPEG-GNP) in B16F10 murine melanoma cells under irradiation of 6 MeV Electron beam. MATERIALS AND METHODS: The synthesized GNP were characterized by UV-Visible spectroscopy, dynamic light scattering, transmission electron microscopy, and zeta potential. Enhancement of radiosensitization was evaluated by the clonogenic assay at different radiation doses of megavoltage electron beams. RESULTS: It was observed that mPEG-GNP with a hydrodynamic size of approximately 50 nm are almost spherical and cellular uptake occurred at all concentrations. Both proliferation efficiency and survival fraction decreased with increasing mPEG-GNP concentration. Furthermore, significant GNP sensitization occurred with a maximum dose enhancement factor of 1.22 at a concentration of 30 µM. CONCLUSIONS: Pegylated-GNP are taken up by B16F10 cancer cells and cause radiosensitization in the presence of 6 MeV electrons. The radiosensitization effects of GNP may probably be due to biological processes. Therefore, the underlying biological mechanisms beyond the physical dose enhancement need to be further clarified.

Enhancing the efficiency of 5-aminolevulinic acid-mediated photodynamic therapy using 5-fluorouracil on human melanoma cells.

BACKGROUND: 5-Aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is an effective and noninvasive modality for treatment of several types of non-melanoma skin cancers. This in-vitro study attempted to know whether the killing effect of ALA-PDT on the human melanoma cells (Mel-Rm cell line) could be increased by the presence of 5-fluorouracil (5-FU). METHODS: To evaluate the effect of ALA-PDT in combination with 5-FU on viability of human melanoma Mel-Rm cells, the cells incubated with 5-ALA and 5-FU for 3h in nontoxic concentrations, and subsequently illuminated with a 630 nm light-emitting diode array. The cells viability and cytotoxicity determined by mitochondrial activity and lactate dehydrogenase assays. RESULTS: Combination of ALA-PDT and 5-FU (FU-ALA-PDT) showed a considerable growth inhibition according to the results of MTT assay compared to ALA-PDT. The results of LDH assay also showed a cytotoxicity effect in ALA-PDT; however, the FU-ALA-PDT showed no significantly enhancement in cytotoxicity compared to ALA-PDT using LDH assay. CONCLUSION: The Mel-Rm cells incubation with 5-FU before PDT enhances the efficiency of 5-Aminolevulinic acid-mediated photodynamic therapy.

Radiosensitization effect of folate-conjugated gold nanoparticles on HeLa cancer cells under orthovoltage superficial radiotherapy techniques.

Due to the high atomic number of gold nanoparticles (GNPs), they are known as new radiosensitizer agents for enhancing the efficiency of superficial radiotherapy techniques by increasing the dose absorbed in tumor cells wherein they can be accumulated selectively. The aim of this study was to compare the effect of various common low energy levels of orthovoltage x-rays and megavoltage γ-rays (Co-60) on enhancing the therapeutic efficiency of HeLa cancer cells in the presence of conjugated folate and non-conjugated (pegylated) GNPs. To achieve this, GNPs with an average diameter of 52 nm were synthesized and conjugated to folic acid molecules. Pegylated GNPs with an average diameter of 47 nm were also synthesized and used as non-conjugated folate GNPs. Cytotoxicity assay of the synthesized folate-conjugated and pegylated GNPs was performed using different levels of nanoparticle concentration incubated with HeLa cells for 24 h. The radiosensitizing effect of both the conjugated and pegylated GNPs on the cells at a concentration of 50 µM was compared using MTT as well as clonogenic assays after exposing them to 2 Gy ionizing radiation produced by an orthovoltage x-ray machine at four different kVps and γ-rays of a Co-60 unit. Significant differences were noted among various irradiated groups with and without the folate conjugation, with an average dose enhancement factor (DEF) of 1.64 ± 0.05 and 1.35 ± 0.05 for the folate-conjugated and pegylated GNPs, respectively. The maximum DEF was obtained with the 180 kVp x-ray beam for both of the GNPs. Folate-conjugated GNPs can significantly enhance the cell killing potential of orthovoltage x-ray energies (especially at 180 kVp) in folate receptor-expressing cancer cells, such as HeLa, in superficial radiotherapy techniques.