Medical Radiation Programme, School of Health Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan,Malaysia.
Material Engineering Programme, School of Materials and Mineral Resources Engineering, Universiti Sains Malaysia, Nibong Tebal, Penang, Malaysia.
Int J Nanomedicine. 2020 Oct 12;15:7805-7823. doi: 10.2147/IJN.S269214. eCollection 2020.
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.
目的:本研究旨在量化氧化铋纳米粒子(BiONPs)、顺铂(Cis)和黄芩素丰富部分(BRF)天然药物与临床放射治疗光子、电子和高剂量率近距离放射治疗束联合应用时产生的协同效应,以及在照射下产生的活性氧(ROS)生成和放射增敏作用。评估了单一化合物和临床放射治疗束在乳腺癌和正常成纤维细胞系中的联合治疗反应。
方法:在这项研究中,在使用 0.38 MeV 铱-192 源、6 MV 光子束和 6 MeV 电子束进行高剂量率近距离放射治疗之前,将单独的 BiONPs、Cis 和 BRF 以及 BiONPs-Cis(BC)、BiONPs-BRF(BB)和 BiONPs-Cis-BRF(BCB)组合应用于细胞。通过量化 MCF-7 和 MDA-MB-231 乳腺癌细胞系以及 NIH/3T3 正常细胞系中 ROS 生成和放射增敏作用,阐明了治疗成分在放射治疗过程中的个体或协同作用。
结果:与 BiONPs 和 BRF 相比,Cis 刺激产生的 ROS 最多。同时,与 brachytherapy 和 electron beam 相比,组件的组合在光子束下诱导了更高的 ROS 水平。与对照相比,BC 组合在 MDA-MB-231 细胞中产生的 ROS 增强最高,而 BB 和 BCB 组合则次之。使用增敏增强比(SER)量化的放射增敏作用表明,在 MCF-7 细胞中,BC 的 SER 值最高,其次是 BCB 和 BB 治疗。与光子和电子束相比,近距离放射治疗的放射增敏作用更为显著。
结论:BiONPs、Cis 和 BRF 是潜在的放射增敏剂,可提高放射治疗的效率,以消灭癌细胞。这些有效放射增敏剂的组合在放射治疗中可能产生多种作用。BC 组合发现具有最高的 SER,其次是 BCB 组合。这项研究也是首次研究 BRF 与 BiONPs(BB)和 BC(BCB)联合治疗的效果。
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