Engineering of Bismuth Oxide Nanoparticles to Induce Differential Biochemical Activity in Malignant and Nonmalignant Cells (original) (raw)

First proof of bismuth oxide nanoparticles as efficient radiosensitisers on highly radioresistant cancer cells

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.

Bismuth Oxide Nanoparticles Induced Oxidative Stress-Related Inflammation in SH-SY5Y Cell Line

Istanbul Journal of Pharmacy

Nanoparticles, chemical structures between 1-100 nm in size, are one of the most promising elements of a new era in technology and science. NPs-based products are growing rapidly in a variety of fields such as health and fitness, electronics and computers, cosmetics, home and garden, food and beverage as well as biomedical applications (Mnyusiwalla et al. 2003; EPA, 2007). The Nanotechnology Consumer Products Inventory report, released in October 2013, listed 1814 nano-containing consumer products, in which the largest group of these products (37%) contains metals and metal oxides NPs (Vance et al. 2015). NPs potentially cause harm to both humans and the environment due to their unique physicochemical properties, size, shape and solubility (Maynard et al. 2006). NPs can easily penetrate the cell membrane due to their very small size and alter the crucial functions of cells. Growing evidence shows that various molecular mechanisms such as DNA damage, oxidative stress, mitochondrial disruption, apoptosis resulting in morphological changes and eventually cell death are responsible for the toxic effects of NPs (Ray et al. 2009; Dhawan and Sharma, 2010; Iavicoli et al. 2013). Bi 2 O 3 is one of the significant metal oxides which has rapidly attracted attention, perhaps because of its use in technology, industry and biomedical sciences (Hyodo et al. 2000; Rabin et al. 2006; Taufik et al. 2011). Despite Bi 2 O 3-NPs widespread usages and the increasing intentional or unintentional exposure, there is limited knowledge about their toxicity (Thomas et al. 2012; Hernandez-Delgadillo et

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

International Journal of Nanomedicine, 2020

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.

Investigation of the bismuth oxide nanoparticles on bystander effect in MCF-7 and hFOB 1.19 cells

Journal of Physics: Conference Series, 2020

This study aims to investigate the effect of bismuth oxide nanoparticles (Bi2O3 NPs) on the radiation induced bystander effect (RIBE) in MCF-7 and hFOB 1.19 cells line. The cells were irradiated with radiation doses of 0 to 12 Gy using 6 MV photon beam in a single exposure. The irradiated cells’ culture media were transferred to non-irradiated bystander cells 1 hour post-irradiation. PrestoBlue assay was then performed in this experiment to assess the cells’ viability. Results of cell viability percentage in all bystander cell groups compared to the control showed no significant differences (P > 0.05) for both MCF-7 and hFOB 1.19 cell lines. The test also revealed no radiation dose dependencies for all bystander cells groups. The present study demonstrated that MCF-7 and hFOB 1.19 bystander cells were able to proliferate (> 80%) after 48 hours incubation with irradiated-cell conditioned medium (ICCM) treated with Bi2O3 NPs. In summary, the use of Bi2O3 NPs for radiosensitizati...

Evaluation of Bismuth Oxide Nanoparticles (BiONPs) as a Safe Radiobiological Enhancer for Breast Cancer Radiotherapy

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...

Effects of Bismuth Oxide Nanoparticles, Cisplatin and Baicalein-rich Fraction on ROS Generation in Proton Beam irradiated Human Colon Carcinoma Cells

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.

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

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.

In vitro cytotoxicity of surface modified bismuth nanoparticles

Journal of Materials Science: Materials in Medicine, 2012

This paper describes in vitro cytotoxicity of bismuth nanoparticles revealed by three complementary assays (MTT, G6PD, and calcein AM/EthD-1). The results show that bismuth nanoparticles are more toxic than most previously reported bismuth compounds. Concentration dependent cytotoxicities have been observed for bismuth nanoparticles and surface modified bismuth nanoparticles. The bismuth nanoparticles are non-toxic at concentration of 0.5 nM. Nanoparticles at high concentration (50 nM) kill 45, 52, 41, 34 % HeLa cells for bare nanoparticles, amine terminated bismuth nanoparticles, silica coated bismuth nanoparticles, and polyethylene glycol (PEG) modified bismuth nanoparticles, respectively; which indicates cytotoxicity in terms of cell viability is in the descending order of amine terminated bismuth nanoparticles, bare bismuth nanoparticles, silica coated bismuth nanoparticles, and PEG modified bismuth nanoparticles. HeLa cells are more susceptible to toxicity from bismuth nanoparticles than MG-63 cells. The simultaneous use of three toxicity assays provides information on how nanoparticles interact with cells. Silica coated bismuth nanoparticles can damage cellular membrane yet keep mitochondria less influenced; while amine terminated bismuth nanoparticles can affect the metabolic functions of cells. The findings have important implications for caution of nanoparticle exposure and evaluating toxicity of bismuth nanoparticles.

Cytotoxicity of biologically synthesised bismuth nanoparticles against HT-29 cell line

IET nanobiotechnology, 2018

This study was purposed to examine the cytotoxicity and functions of biologically synthesised bismuth nanoparticles (Bi NPs) produced by sp. SFG on human colon adenocarcinoma cell line of HT-29. The structural properties of Bi NPs were investigated using transmission electron microscopy, energy dispersive X-ray, and X-ray diffraction techniques. The cytotoxic effects of Bi NPs were analysed using flow cytometry cell apoptosis while western blot analyses were applied to analyse the cleaved caspase-3 expression. Oxidative stress (OS) damage was determined using the measurement of the glutathione (GSH) and malondialdehyde (MDA) levels and antioxidant activity of superoxide dismutase (SOD) and catalase (CAT) levels. The half maximal inhibitory concentration (IC) value of Bi NPs was measured to be 28.7 ± 1.4 µg/ml on HT-29 cell line. The viability of HT-29 represented a concentration-dependent pattern (5-80 µg/ml). The mode of Bi NPs induced apoptosis was found to be mainly related to la...

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...