Synergetic radiosensitization effects of bismuth oxide nanoparticles, cisplatin and baicalein-rich fraction from oroxylum indicum combinations for clinical radiotherapy
Year: 2021
Type: dissertation
Abstract: Multimodal strategies of cancer treatment aim to eradicate complex malignant \ndisease with enhanced therapeutic outcome with combined synergetic effects in \ncontrast to individual techniques that might exhibits some limitations. \nChemotherapeutic drug such as cisplatin have been applied to increase radiation doses \nat target tissues in radiotherapy. However, commercial chemo-drugs toxicities had \ncompelled the researchers to evaluate alternatives for non-toxic agents and \nradiosensitizers, potentially from natural derivatives or metal-based nanoparticles \n(NPs). Integration of novel nanomaterials and natural product as radiosensitizer to \nincrease the anti-tumors efficacy are also promising to enhance the treatment \nperformance. This study aimed to investigate the synergetic radiosensitization effects \nof bismuth oxide NPs (BiONPs), cisplatin (Cis) and a baicalein-rich fraction (BRF) \nfrom Oroxylum indicum (OI) leaves extract under clinical radiotherapy of High Dose \nRate (HDR) brachytherapy, photon, and electron beams. The cytotoxicity, cellular \nuptake, and reactive oxygen species (ROS) generation induced by BiONPs were \ninitially investigated on MCF-7 and MDA-MB-231 breast cancer as well as NIH/3T3 \nnormal fibroblast cell lines in elucidating the BiONPs feasibility for radiotherapy \napplication. The safe concentration of Cis and BRF were also determined prior \nirradiation. Quantification of radiosensitization effects and ROS generation were \nconducted with individual BiONPs, Cis, and BRF, as well as BiONPs-Cis (BC), \nBiONPs-BRF (BB) and BiONPs-Cis-BRF (BCB) combinations for High Dose Rate \n(HDR) brachytherapy, photon, and electron beams. Raman Spectroscopy and \napoptosis analysis were conducted to elucidate the subcellular biochemical changes \nand cells death mechanism. The cytotoxicity results provide that the BiONPs induced \nminimal cell deaths constituting less than 20% on average while ROS production by \nBiONPs was negligible. The increment of NPs cellular uptake indicated that BiONPs \nwere internalized and bound to the cellular surfaces. Consequently, 0.5 mM of 60 nm \nBiONPs was found to be an optimum concentration and size for radiotherapy \napplication. The lowest values of the 25% of inhibition concentration by individual \nCis and BRF obtained were 1.30 μM and 0.76 μg/ml, respectively, and utilized for the \nsubsequent experiments. Investigation of the radiosensitization effects among the \ntreatment components indicated the highest SER value by BC combination in MCF-7 \ncells, followed by BCB and BB treatments. The effects were more prominent for Ir- \n192 of γ-radiation compared to photon and electron beams. Meanwhile, the \ncombination treatments present the higher ROS levels for photon beam than \nbrachytherapy and electron beam. The highest ROS enhancement was attributed to the \npresence of BC combination in MDA-MB-231 cells. Interestingly, the BCB \ncombination also showed a high SER but collaterally affected the normal cells. The \nBC combination of MCF-7 cells showed potential as an effective radiosensitizer for \nbrachytherapy with the early apoptosis predominantly occurred within 40 hours after \nirradiation. Finally, the finding from Raman spectroscopy demonstrated that the \nBiONPs-Cis and brachytherapy combination would affect the glycolysis process, the \namino acid structure arrangement and the DNA/RNA stability that would suggest the \nenhancement of radiation effects on cancer cells. In conclusion, this study suggests the \npotential of BiONPs, Cis and BRF as radiosensitizer that could improve the efficiency \nof radiotherapy to eradicate the cancer cells. The combination of these potent \nradiosensitizers could produce synergetic effects that will elevate the therapeutic \nimpact of clinical radiotherapy.
Author: Sisin, Noor Nabilah Talik
Language: English
Subfield: Radiation
Field: Physics and Astronomy
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7024990358