Natural Baicalein-Rich Fraction as Radiosensitizer in Combination with Bismuth Oxide Nanoparticles and Cisplatin for Clinical Radiotherapy.

Purpose: Chemotherapy has been used in conjunction with radiation therapy to improve the treatment outcomes of cancers. Cisplatin (Cis) is a standard treatment that has been used as a chemotherapeutic drug in medical settings. However, the possibility of complications constrains the treatment due to the exposure of healthy organs to unnecessary radiation and the drugs' toxicities. As a result, researchers have been looking for non-toxic chemotherapeutic agents which can be used as radiosensitizers, possibly produced from natural derivatives and nano sized materials. Methods: BRF, Cis, and BiONPs were irradiated individually and in combinations with 6 MV of photon beam and 6 MeV of electron beams with 0 to 10 Gy radiation doses on MCF-7, MDA-MB-231, and NIH/3T3 cell lines. Then, the experimental sensitization enhancement ratios (SER) of each treatment obtained were compared to the theoretical dose enhancement factor (DEF). The interactions within the BRF-BiONPs (BB) and BRF-Cis-BiONPs (BCB) combinations were also estimated using the Combination Index (CI). Results: BRF induced radiosensitization in all cells under 6 MV photon beam (SER of 1.06 to 1.35), and MDA-MB-231 cells only under 6 MeV electron beam (SER = 1.20). The highest SER values for BiONPs and Cis were obtained from MCF-7 cells under a 6 MeV electron beam (SER of 1.50 and 2.24, respectively). The theoretical DEFs were generally lower than the experimental SERs. Based on the SER and CI relationships, it was estimated that BB and BCB therapy methods interacted in either a synergistic or additive manner. Conclusion: The BRF is found to induce relatively less radiosensitization effects compared to the BiONPs and Cis. The BB and BCB combinations have shown better effects with potential for becoming competently suitable radiosensitizers in breast cancer therapies.

Radiosensitization effects by bismuth oxide nanorods of different sizes in megavoltage external beam radiotherapy.

BACKGROUND: Nanotechnology application has successfully reached numerous scientific breakthroughs including in radiotherapy. However, the clinical application of nanoparticles requires more diligent research primarily on the crucial parameters such as nanoparticle sizes. This study is aimed to investigate the influence of bismuth oxide nanorod (Bi2O3-NR) sizes on radiosensitization effects on MCF-7 and HeLa cell lines for megavoltage photon and electron beam radiotherapy. MATERIALS AND METHODS: MCF-7 and HeLa cells were treated with and without 0.5 µMol/L of Bi2O3-NR of varying sizes (60, 70, 80, and 90 nm). The samples, including the control groups, were exposed to different radiation doses (0-10 Gy), using photon (6 MV and 10 MV), and electron beam (6 MeV and 12 MeV) radiotherapy. Clonogenic assay was performed, and sensitization enhancement ratio (SER) was determined from linear quadratic based cell survival curves. RESULTS: The results depicted that 60 nm Bi2O3-NR yields the most excellent SER followed by 70 nm Bi2O3-NR. Meanwhile, the 80 and 90 nm Bi2O3-NR showed an insignificant difference between treated and untreated cell groups. This study also found that MCF-7 was subjected to more cell death compared to HeLa. CONCLUSION: 60 nm Bi2O3-NR was the optimal Bi2O3-NR size to induce radiosensitization effects for megavoltage external beam radiotherapy. The SER in photon beam radiotherapy marked the highest compared to electron beam radiotherapy due to decreased primary radiation energy from multiple radiation interaction and higher Compton scattering.

Synergetic Influence of Bismuth Oxide Nanoparticles, Cisplatin and Baicalein-Rich Fraction on Reactive Oxygen Species Generation and Radiosensitization Effects for Clinical Radiotherapy Beams.

PURPOSE: This study aimed to quantify synergetic effects induced by bismuth oxide nanoparticles (BiONPs), cisplatin (Cis) and baicalein-rich fraction (BRF) natural-based agent on the reactive oxygen species (ROS) generation and radiosensitization effects under irradiation of clinical radiotherapy beams of photon, electron and HDR-brachytherapy. The combined therapeutic responses of each compound and clinical radiotherapy beam were evaluated on breast cancer and normal fibroblast cell line. METHODS: In this study, individual BiONPs, Cis, and BRF, as well as combinations of BiONPs-Cis (BC), BiONPs-BRF (BB) and BiONPs-Cis-BRF (BCB) were treated to the cells before irradiation using HDR brachytherapy with 0.38 MeV iridium-192 source, 6 MV photon beam and 6 MeV electron beam. The individual or synergetic effects from the application of the treatment components during the radiotherapy were elucidated by quantifying the ROS generation and radiosensitization effects on MCF-7 and MDA-MB-231 breast cancer cell lines as well as NIH/3T3 normal cell line. RESULTS: The ROS generated in the presence of Cis stimulated the most substantial amount of ROS compared to the BiONPs and BRF. Meanwhile, the combination of the components had induced the higher ROS levels for photon beam than the brachytherapy and electron beam. The highest ROS enhancement relative to the control is attributable to the presence of BC combination in MDA-MB-231 cells, in comparison to the BB and BCB combinations. The radiosensitization effects which were quantified using the sensitization enhancement ratio (SER) indicate the highest value by BC in MCF-7 cells, followed by BCB and BB treatment. The radiosensitization effects are found to be more prominent for brachytherapy in comparison to photon and electron beam. CONCLUSION: The BiONPs, Cis and BRF are the potential radiosensitizers that could improve the efficiency of radiotherapy to eradicate the cancer cells. The combination of these potent radiosensitizers might produce multiple effects when applied in radiotherapy. The BC combination is found to have the highest SER, followed by the BCB combination. This study is also the first to investigate the effect of BRF in combination with BiONPs (BB) and BC (BCB) treatments.

Radiosensitization Effects by Bismuth Oxide Nanoparticles in Combination with Cisplatin for High Dose Rate Brachytherapy.

PURPOSE: The aim of this study was to investigate the potential of the synergetic triple therapeutic combination encompassing bismuth oxide nanoparticles (BiONPs), cisplatin (Cis), and high dose rate (HDR) brachytherapy with Ir-192 source in breast cancer and normal fibroblast cell line. METHODS: In vitro models of breast cancer cell lines (MCF-7, MDA-MB-231) and normal fibroblast cell line (NIH/3T3) were employed. Cellular localization and cytotoxicity studies were conducted prior to inspection on the radiosensitization effects and generation of reactive oxygen species (ROS) on three proposed radiosensitizers: BiONPs, Cis, and BiONPs-Cis combination (BC). The optimal, non-cytotoxic concentration of BiONPs (0.5 mM) and the 25% inhibitory concentration of Cis (1.30 µM) were applied. The radiosensitization effects were evaluated by using a 0.38 MeV Iridium-192 HDR brachytherapy source over a prescribed dose range of 0 Gy to 4 Gy. RESULTS: The cellular localization of BiONPs was visualized by light microscopy and accumulation of the BiONPs within the vicinity of the nuclear membrane was observed. Quantification of the sensitization enhancement ratio extrapolated from the survival curves indicates radiosensitization effects for MCF-7 and MDA-MB-231 when treated with BiONPs, Cis, and BC. However, NIH/3T3 cells exhibited contradictive behavior as it only reacted towards the BC combination. Nonetheless, the MCF-7 cell line loaded with BC shows the highest SER of 4.29. ROS production analysis, on the other hand, shows that Cis and BC radiosensitizers generated the highest free radicals in comparison to BiONPs alone. CONCLUSION: A BiONPs-Cis combination was unveiled as a novel approach that offers promising radiosensitization enhancement that will increase the efficiency of tumor control while preserving the normal tissue at a reduced dose. This data is the first precedent to prove the synergetic implication of BiONPs, Cis, and HDR brachytherapy that will be beneficial for future chemoradiotherapy strategies in cancer care.

Effect of scanning parameters on dose-response of radiochromic films irradiated with photon and electron beams.

Proper dosimetry settings are crucial in radiotherapy to ensure accurate radiation dose delivery. This work evaluated scanning parameters as affecting factors in reading the dose-response of EBT2 and EBT3 radiochromic films (RCFs) irradiated with clinical photon and electron beams. The RCFs were digitised using Epson® Expression® 10000XL flatbed scanner and image analyses of net optical density (netOD) were conducted using five scanning parameters i.e. film type, resolution, image bit depth, colour to grayscale transformation and image inversion. The results showed that increasing spatial resolution and deepening colour depth did not improve film sensitivity, while grayscale scanning caused sensitivity reduction below than that detected in the Red-channel. It is also evident that invert and colour negative film type selection negated netOD values, hence unsuitable for scanning RCFs. In conclusion, choosing appropriate scanning parameters are important to maintain preciseness and reproducibility in films dosimetry.

Optimal energy for cell radiosensitivity enhancement by gold nanoparticles using synchrotron-based monoenergetic photon beams.

Gold nanoparticles have been shown to enhance radiation doses delivered to biological targets due to the high absorption coefficient of gold atoms, stemming from their high atomic number (Z) and physical density. These properties significantly increase the likelihood of photoelectric effects and Compton scattering interactions. Gold nanoparticles are a novel radiosensitizing agent that can potentially be used to increase the effectiveness of current radiation therapy techniques and improve the diagnosis and treatment of cancer. However, the optimum radiosensitization effect of gold nanoparticles is strongly dependent on photon energy, which theoretically is predicted to occur in the kilovoltage range of energy. In this research, synchrotron-generated monoenergetic X-rays in the 30-100 keV range were used to investigate the energy dependence of radiosensitization by gold nanoparticles and also to determine the photon energy that produces optimum effects. This investigation was conducted using cells in culture to measure dose enhancement. Bovine aortic endothelial cells with and without gold nanoparticles were irradiated with X-rays at energies of 30, 40, 50, 60, 70, 81, and 100 keV. Trypan blue exclusion assays were performed after irradiation to determine cell viability. Cell radiosensitivity enhancement was indicated by the dose enhancement factor which was found to be maximum at 40 keV with a value of 3.47. The dose enhancement factor obtained at other energy levels followed the same direction as the theoretical calculations based on the ratio of the mass energy absorption coefficients of gold and water. This experimental evidence shows that the radiosensitization effect of gold nanoparticles varies with photon energy as predicted from theoretical calculations. However, prediction based on theoretical assumptions is sometimes difficult due to the complexity of biological systems, so further study at the cellular level is required to fully characterize the effects of gold nanoparticles with ionizing radiation.

Polymer gels impregnated with gold nanoparticles implemented for measurements of radiation dose enhancement in synchrotron and conventional radiotherapy type beams.

Normoxic type polyacrylamide gel (nPAG) dosimeters are established for dose quantification in three-dimensions for radiotherapy and hence represent an adequate dosimeter for quantification of the dose variation due to the existence of the gold nanoparticles (AuNPs) in the target during irradiation. This work compared the degree of polymerisation in gel doped with nanoparticles (nPAG-AuNP) with control gel samples when irradiated by various sources. Samples were irradiated with a synchrotron radiation source of mean energy 125 keV, 80 kV X-ray beams from superficial therapy machine (SXRT), 6 MV X-rays and 6 MeV electron beams from linear accelerator. Analysis of the dose-response relation was used to determine a dose enhancement factor (DEF) of 1.76 ± 0.34 and 1.64 ± 0.44 obtained for samples irradiated with kilovoltage X-rays energy from synchrotron source and SXRT respectively. Similarly, including AuNPs in gel results in a DEF of approximately 1.37 ± 0.35 when irradiated by an electron beam and 1.14 ± 0.28 for high energy X-ray beams. The results demonstrate the use of AuNPs embedded in polymer gels for measuring the enhancement of radiation caused by metallic nanoparticles.

Potential dependent superiority of gold nanoparticles in comparison to iodinated contrast agents.

PURPOSE: To identify the benefits in image contrast enhancement using gold nanoparticles (AuNPs) compared to conventional iodinated contrast media. MATERIALS AND METHODS: Gold nanoparticles and iodinated contrast media were evaluated for contrast enhancement at various X-ray tube potentials in an imaging phantom. Iopromide and AuNP suspension were equalized according to molar concentration of radiopaque element (0.5077 Mol/L). Contrast-to-noise ratio is used to quantify contrast enhancement. Both projectional radiographic (40-80 kVp) and computed tomography (CT) (80-140 kVp) imaging modalities were examined. RESULTS AND CONCLUSIONS: Findings indicate 89% improvement in CNR at low energies near the mammographic range (40 kVp). However, as expected no significant difference in enhancement was observed at potentials commonly used for angiography (around 80 kVp) probably due to the k-edge influence for iodine. At the highest energies typically available in computed tomography, significant improvement in contrast enhancement using gold nanoparticles is obtained, 114% greater CNR than that produced by iodine at 140 kVp. Experimental findings for 70-120 kVp spectra correlate well with the theoretical calculations based on linear attenuation coefficients. Superior attenuation of gold nanoparticles at low and high kVp potentials support their further (pre)clinical evaluation.

Enhancement of radiation effects by gold nanoparticles for superficial radiation therapy.

Iodinated contrast agents, which are routinely used to improve contrast in x-ray diagnostic radiography, have been successfully proven to enhance radiation effects in kilovoltage x-ray radiation therapy beams. The studies determined the influence of iodine on the level of radiation biotoxicity to cells as an indicator of the radiation dose enhancement. The use of other high-atomic-number materials such as gold nanoparticles (AuNPs) may also provide advantages in terms of radiation dose enhancement. In this work AuNPs have been used for the enhancement of radiation effects on bovine aortic endothelial cells of superficial x-ray radiation therapy and megavoltage electron radiation therapy beams. Results reveal an increase of cell damage with increasing concentration of AuNPs. At 1 mM concentration of AuNPs, enhancement of radiation peaked at 25 times for a kilovoltage x-ray beam. AuNPs showed similar effects on electron beams but to a lesser extent. This study showed that AuNPs can be used to enhance the effect of radiation doses from kilovoltage x-ray radiation therapy and megavoltage electron radiation therapy beams. In the prevailing clinical circumstances, wherein radiation therapy dose is constrained by normal tissue tolerance, this enhancement could in the future be used to improve local control in superficial x-ray treatments, megavoltage electron beam radiation therapy, microbeam radiation therapy, and intraoperative irradiation using kilovoltage x-rays or megavoltage electron beams. Moreover, the value of this work also stems from the fact that the damage to the endothelial cells lining the highly vasculature structure of tumors deprives tumors of their oxygen and nutrients supply and enhances the efficiency of radiation therapy treatment, where it has been proven that more of the AuNPs injected into animals ends up into the blood than in the tumor.