Synergetic Influence of Bismuth Oxide Nanoparticles, Cisplatin and Baicalein-Rich Fraction on Reactive Oxygen Species Generation and Radiosensitization Effects for Clinical Radiotherapy Beams (original) (raw)
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International Journal of Nanomedicine, 2019
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.
International Journal of Nanomedicine
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.
Polish Journal of Medical Physics and Engineering, 2022
Introduction: Proton beam radiotherapy is an advanced cancer treatment technique, which would reduce the effects of radiation on the surrounding healthy cells. The usage of radiosensitizers in this technique might further elevate the radiation dose towards the cancer cells. Material and methods: The present study investigated the production of intracellular reactive oxygen species (ROS) due to the presence of individual radiosensitizers, such as bismuth oxide nanoparticles (BiONPs), cisplatin (Cis) or baicaleinrich fraction (BRF) from Oroxylum indicum plant, as well as their combinations, such as BiONPs-Cis (BC), BiONPs-BRF (BB), or BiONPs-Cis-BRF (BCB), on HCT-116 colon cancer cells under proton beam radiotherapy. Results: It was found that the ROS in the presence of Cis at 3 Gy of radiation dose was the highest, followed by BC, BiONPs, BB, BRF, and BCB treatments. The properties of bismuth as a radical scavenger, as well as the BRF as a natural compound, might contribute to the lower intracellular ROS induction. The ROS in the presence of Cis and BC combination were also time-dependent and radiation dose-dependent. Conclusions: As the prospective alternatives to the Cis, the BC combination and individual BiONPs showed the capacities to be developed as radiosensitizers for proton beam therapy.
Radiation Physics and Chemistry, 2020
Background: Nanomaterials have been applied as radiosensitizer in an effort to improve the effectiveness of radiotherapy in killing cancer cells while simultaneously sparing the healthy normal tissue. Increase in radiotoxicity to the cancerous region might also influence the non-targeted cells through radiation-induced bystander effect (RIBE) mechanism. In this study, we implemented Bi 2 O 3 NPs as radiosensitizer in combination with megavoltage radiotherapy and probe into the RIBE consequences in the non-targeted cells. Aim: To investigate the effects of bismuth oxide nanoparticles (Bi 2 O 3 NPs) on RIBE triggered in MCF-7 and hFOB 1.19 after irradiation with 10 MV clinical photon beam. Materials and methods: The MCF-7 (human breast cancer) and hFOB 1.19 (human fetal osteoblast) cell lines were incubated with and without Bi 2 O 3 NPs prior to irradiation. The treated cells were irradiated with radiation doses of 0 to 12 Gy using 10 MV photon beam in a single exposure. The irradiated-cell conditioned medium (ICCM) were collected from the targeted cells and transferred into the non-targeted cells. Reactive oxygen species (ROS), cell viability and colony forming assay was employed to evaluate the effect. Results: The present study demonstrated that the MCF-7 and hFOB 1.19 bystander cells are able to maintain their cell viability for more than 80% after 48 h incubation with ICCM treated with Bi 2 O 3 NPs at 2 Gy radiation dose. The percentage of cell survival fraction of hFOB 1.19 cells which received ICCM with Bi 2 O 3 NPs decreased to 86.8%, in contrast to MCF-7 bystander cells which show an increment in their cells survival after treatment with Bi 2 O 3 NPs. Our results show that the ROS level was increased in the bystander cells, but the addition of Bi 2 O 3 NPs did not significantly increase the ROS level. Conclusions: The application of nanoparticles for radiosensitization during radiotherapy must also considered the RIBE responses in the non-irradiated cells. These findings provide evidence that the use Bi 2 O 3 NPs as radiosensitizer in radiotherapy is safe and do not significantly increase the RIBE responses in non-targeted cells.
Potential of radiosensitizing agents in cancer chemo-radiotherapy
Journal of Cancer Research and Therapeutics, 2005
Potential of herbs and other plant-based formulations have been increasingly recognized in prevention and treatment of human diseases including cancer. There exist enormous prospect for screening and evaluation of herbal/plant products for developing effective radiosensitization and radioprotection relevant to nuclear research program. Investigations in our laboratory have focused on the mechanism of activity of variety of anticancer and antioxidant agents, namely, Eugenol, (EU), Ellagic acid (EA), Triphala (TPL), Tocopherol Succinate (TOS) and Arachidonic acid on normal and cancer cells with view to design effective protocols in practical radioprotection and cancer radiotherapy. This paper is mainly focused on studies on cytotoxic effects on cancer cell lines. Results have shown that these agents produced radiosensitizing action involving oxidative damage, membrane alteration and damage to nucleic acid in various human cell lines. Studies were performed employing fluorescence probes and electron spin resonance methods and gel electrophoresis protocols. It has been found that cytotoxic effect was induced by initiating membrane oxidative damage and by triggering intracellular generation of reactive oxygen species (ROS) by gamma radiation in combination with phytochemicals like TPL, EA and TOS in tumor cell line Ehrlich Ascites (EAC), Human cervical (HeLa) and breast (MCF-7) cells. Membrane damage and ROS generation was measured by DPH and DCF-FDA fluorescent probes respectively after exposure to low to moderate doses of gamma radiation. This talk will present the cytotoxic effects of phytochemicals in combination with ionizing radiation. It is emphasized that modulation of membrane peroxidative damage and intra cellular ROS may help achieve efficient killing of cancer cells which may provide a new approach to developing effective treatment of cancer.
Asian Journal of Medicine and Biomedicine
Cancer incidence has been increasing over the years and it is the second leading cause of death globally [1]. The therapeutic strategies in killing the cancerous tissue while keeping the normal healthy tissue uninterrupted can be further improved by introducing nanoparticles (NPs) as radiosensitizers in radiotherapy. In pre-clinical research, a few nanoparticle elements had shown the potential to be radiosensitizers, such as gold, superparamagnetic iron oxide, platinum, and bismuth nanoparticles. Bismuth oxide nanoparticles (BiONPs) have been investigated as a potential radiosensitizer in radiotherapy due to their least toxic and biocompatibility properties. In addition, due to the presence of metallic nanoparticles in cells and their environment, more DNA damage will be introduced and thus enhance the radiation treatment efficacy. This research project was conducted to evaluate the potential of BiONPs to increase the radiation treatment in MCF-7 breast cancer cells and their side...
Dose enhancement by bismuth oxide nanoparticles for HDR brachytherapy
Journal of Physics: Conference Series, 2020
Escalation of biological damage through the induction of dose enhancement effect in radiotherapy cancer treatment by high-Z nanoparticles (NPs) has recently been the subject of growing interest. Hence, this study was conducted primarily to investigate the enhancement of brachytherapy (source Ir192) efficacy by bismuth oxide nanoparticles (BiONPs) on cervical cancer cells. Radiosensitization effect was tested against different size and concentration of BiONPs. After irradiation with radiation doses ranging from 0 to 4 Gy, the survival of the cell was quantified by clonogenic assay and presented in survival curves fitted using the LQ model. Dose enhancement (DE) factor was extrapolated from the curve at 50% of cell survival and calculated. The results marked out the dependency of DE on nanoparticles size and concentrations. The optimum size of BiONPs was found to be 80 nm with a concentration of 0.00025 mM, in which the DEF is 1.88. In conclusion, this study suggests that the inductio...
Journal of Radiation Research, 2001
LQ analysis/Bromodeoxyuridine (BrdUrd)/Hyperthermia/Radiosensitization/Human tumor cells. Sensitization by bromodeoxyuridine (BrdUrd) and hyperthermia (HT) on cell reproductive death induced by ionizing radiation was analyzed using the linear-quadratic [S(D)/S(0)=exp{-(αD+βD 2)}] model. Plateau-phase human lung tumor cells (SW-1573) and human colorectal carcinonoma cells (RKO) were treated with BrdUrd, radiation and HT. LQ-analysis was performed at iso-incubation dose and at iso-incorporation level of BrdUrd, and at iso-HT doses and iso-survival levels after HT. Clonogenic assays were performed 24 h after treatment to allow repair of potentially lethal damage (PLD). In SW cells BrdUrd, HT or the combination significantly increased the α-parameter (factor 2.0-5.7), without altering the β-parameter. In RKO cells sensitization with BrdUrd increased both α (factor 1.4) and β (factor 1.3) while HT only influenced β (factor 2.1-4.0). The combination did not further increase the α and β. The results indicate that BrdUrd has its main effect on the parameter α, dominant at clinically relevant radiation doses but that HT can affect both α and β. The addition of BrdUrd and HT provides a method to enhance the efficacy of radiotherapy.
Influence of PEG-coated Bismuth Oxide Nanoparticles on ROS Generation by Electron Beam Radiotherapy
Polish Journal of Medical Physics and Engineering
Introduction: Nanoparticles (NPs) have been proven to enhance radiotherapy doses as radiosensitizers. The introduction of coating materials such as polyethylene glycol (PEG) to NPs could impact the NPs’ biocompatibility and their effectiveness as radiosensitizers. Optimization of surface coating is a crucial element to ensure the successful application of NPs as a radiosensitizer in radiotherapy. This study aims to investigate the influence of bismuth oxide NPs (BiONPs) coated with PEG on reactive oxygen species (ROS) generation on HeLa cervical cancer cell line. Material and methods: Different PEG concentrations (0.05, 0.10, 0.15 and 0.20 mM) were used in the synthesis of the NPs. The treated cells were irradiated with 6 and 12 MeV electron beams with a delivered dose of 3 Gy. The reactive oxygen species (ROS) generation was measured immediately after and 3 hours after irradiation. Results: The intracellular ROS generation was found to be slightly influenced by electron beam energy...
Physica Medica, 2016
This study provides the first proof of the novel application of bismuth oxide as a radiosensitiser. It was shown that on the highly radioresistant 9L gliosarcoma cell line, bismuth oxide nanoparticles sensitise to both kilovoltage (kVp) or megavoltage (MV) X-rays radiation. 9L cells were exposed to a concentration of 50 μg.mL −1 of nanoparticle before irradiation at 125 kVp and 10 MV. Sensitisation enhancement ratios of 1.48 and 1.25 for 125 kVp and 10 MV were obtained in vitro, respectively. The radiation enhancement of the nanoparticles is postulated to be a combination of the high Z nature of the bismuth (Z = 83), and the surface chemistry. Monte Carlo simulations were performed to elucidate the physical interactions between the incident radiation and the nanoparticle. The results of this work show that Bi 2 O 3 nanoparticles increase the radiosensitivity of 9L gliosarcoma tumour cells for both kVp and MV energies. Monte Carlo simulations demonstrate the advantage of a platelet morphology.