Evaluation of Bismuth Oxide Nanoparticles as Radiosensitizer for Megavoltage Radiotherapy

Abstract

Metal-based nanoparticles such as gold, silver, platinum, and bismuth have been widely investigated for radiotherapeutic application. Basic understanding of the cellular interaction of the nanoparticles with the biological materials is crucial to ensure future clinical use. In this study, the cytotoxicity, cellular uptake, and generation of reactive oxygen species (ROS) induced by BiONPs were investigated prior elucidating the feasibility of BiONPs for radiotherapy application using megavoltage photon and electron beams. The BiONPs of diameter sizes 60, 70, 80 and 90 nm at concentrations within a range of 0.5 to 0.00005 mMol/L were tested on MCF-7, MDA-MB-231, and NIH/3T3 cells lines. The cytotoxicity results exhibit minimal cell death constituting less than 20 % of mortality on average. The ROS generation by BiONPs alone is found to be negligible as the ROS levels were slightly lower and higher than 100% of positive control. The increment of cellular nanoparticles uptake from a range of 1.50 % to 34.10 % indicates that BiONPs were internalized and bound to the surface of the cells. Sequencing from the results, 60 nm BiONPs are found to be the most suitable to be applied as a radiosensitizer in radiotherapy. Sensitization enhancement ratio (SER) quantified on MCF-7 cells demonstrated the highest enhancement from the highest concentration of BiONPs with SER of 2.29 and 1.42, for 10 MV photon beam and 6 MeV electron beam, respectively. In contrast to ROS production without radiation, the ROS induced from radiotherapy beams were found to be dose-dependent and play significant roles in radiosensitization effect. In conclusion, BiONPs could improve clinical radiotherapy, and further radiobiological characterization is crucial for future clinical translation.

<p>Radiosensitization Effects by Bismuth Oxide Nanoparticles in Combination with Cisplatin for High Dose Rate Brachytherapy</p>

“…The BiONPs have been observed surrounding the nuclei or scattered in the cytoplasm, which proves BiONPs penetration into the cells. In our recently published work, the BiONPs uptake into the cells was demonstrated quantitatively using flow cytometry gating, in which the high Q2 quadrant percentage for treatment of BiONPs onto the cells indicated the cellular uptakes of BiONPs 25. Theoretically, the BiONPs could enter the cells through macropinocytosis pathway, which is a cell transport system with a minimum of 0.5 µm vesicular size 26.…”

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

“…In a previous study, we have conducted in vitro cytotoxic effect which concluded the 0.5 mM as the biocompatible concentration used in this study. 13 Cisplatin (Cis) (Tokyo Chemical Industry) was prepared as 41.7 µM in dimethyl sulfoxide (DMSO) (Fisher Scientific) solvent and stored at −20°C. Cis was treated onto the cells to a final concentration of 1.30 µM within the well, based on the cytotoxicity assay in our recently published work.…”

“…The model is represented by the linear component [exp (-αD)], which is designated for a single hit to the double-strand of DNA breakage and a quadratic component [exp (-βD2)] which denoted the double hits that induce double-strand damage of the chromosomes. 12,13 The sensitization enhancement ratio (SER) was extrapolated from the LQ graph fittings. The values indicated the radiosensitization effect by each treatment component and were calculated using the formula as in Equation 4.…”

“…108 However, this case was contradictory to our previous work of the uncoated-BiONPs on the MCF-7 cells, in which 6 MV photon had been induced the SER of 1.88 while 6 MeV generated the SER of 1.42. 13 The different findings may indicate that the functionalization of BiONPs with PEG would lower the radiosensitization effects in MCF-7 cells. The presence of Cis in the BC treatment might have reacted similarly to the PEG coating.…”

“…[8][9][10] Several prior studies had established that gold and bismuth oxide NPs could be the radiosensitizers for some clinical radiotherapy modalities such as photon beam (6 and 10 MV), electron beam (6 and 15 MeV) and brachytherapy with iridium-192 (Ir-192) source. [11][12][13][14] Apart from gold and bismuth oxide NPs, platinum and superparamagnetic iron oxide NPs (SPIONs) also had the potential to be a radiosensitizer, as our previous research on the four types of NPs under 150 MeV proton beam found to have sensitization enhancement ratio (SER) values of 1.95 to 4.93. 15 The dendrite-shaped platinum NPs with the sizes of 29 to 52 nm were also discovered to cause the radiosensitization effect with SER of 1.77 to 2.31 for photon beam radiotherapy, while a smaller size of platinum NPs (1.7 nm) demonstrated the amplification of the effect from cobalt-60 radiation by 37%.…”