Evaluation of Bismuth Oxide Nanoparticles as Radiosensitizer for Megavoltage Radiotherapy

Noor Nabilah Talik Sisin, Safri Zainal Abidin, Yunus Muhammad Amir, M. Zin Hafiz, Khairunisak Abdul Razak, Wan Nordiana Rahman

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.


Keywords


bismuth oxide nanoparticles; cytotoxicity; reactive oxygen species; radiotherapy.

Full Text:

PDF

References


B. Bhushan, “Introduction to Nanotechnology,†in Springer Handbook of Nanotechnology, B. Bhushan, Ed. Springer-Verlag Berlin Heidelberg, 2010, pp. 1–13.

K. K. Jain, The Handbook of Nanomedicine, 3rd ed. Humana Press, 2008.

L. Cui, “Optimization of Gold Nanoparticle Radiosensitizers for Cancer Therapy Optimization of Gold Nanoparticle Radiosensitizers,†University of Toronto, 2016.

S. Alarifi, D. Ali, S. Alkahtani, and M. S. Alhader, “Iron oxide nanoparticles induce oxidative stress, DNA damage, and caspase activation in the human breast cancer cell line,†Biol. Trace Elem. Res., vol. 159, no. 1–3, pp. 416–424, 2014.

B. Liu, L. Ezeogu, L. Zellmer, B. Yu, N. Xu, and D. Joshua Liao, “Protecting the Normal in Order to Better Kill the Cancer.,†Cancer Med., vol. 4, no. 9, pp. 1394–403, 2015.

W. N. Rahman, S. Corde, N. Yagi, S. A. Abdul Aziz, N. Annabell, and M. Geso, “Optimal Energy for Cell Radiosensitivity Enhancement by Gold Nanoparticles using Synchrotron-based Monoenergetic Photon Beams,†Int. J. Nanomedicine, vol. 9, no. 1, pp. 2459–2467, 2014.

L. Cui, S. Her, M. Dunne, G. R. Borst, R. D. Souza, R. G. Bristow, D. A. Jaffray, C. Allen, “Significant Radiation Enhancement Effects by Gold Nanoparticles in Combination with Cisplatin in Triple Negative Breast Cancer Cells and Tumor Xenografts,†Radiat. Res., vol. 187, no. 2, pp. 147–160, 2017.

M. J. Eblan and A. Z. Wang, “Improving chemoradiotherapy with nanoparticle therapeutics.†Transl. Cancer Res., vol. 2, no. 4, pp. 320–329, 2013.

J. J. Zhu, J. J. Shan, L. B. Sun, and W. S. Qiu, “Study of the radiotherapy sensitization effects and mechanism of capecitabine (Xeloda) against non-small-cell lung cancer cell line A549,†Genet. Mol. Res., vol. 14, no. 4, pp. 16386–16391, 2015.

W. D. Oliver, A. P. Duffy, and P. F. Hausner, “Case report of capecitabine toxicity and use of uridine triacetate,†J. Oncol. Pharm. Pract., vol. 25, no. 2, pp. 470–473, 2019.

L. Fernandez, A. Dominguez, W. Martinez, F. Sanabria, C. S. Leib, and B. R. G. in Thorax., “Pulmonary Toxicity Due to 5-Fluorouracil (5-FU) Manifested as Diffuse Alveolar Hemorrhage: Case Report,†in D34. Lung Transplant and Drug Induced Lung Disease: Case Reports, 2018.

H. Yang, C. Liu, D. Yang, H. Zhang, and Z. Xi, “Comparative study of cytotoxicity, oxidative stress and genotoxicity induced by four typical nanomaterials: The role of particle size, shape and composition,†J. Appl. Toxicol., vol. 29, no. 1, pp. 69–78, 2009.

A. L. Vega-Jiménez et al., “Bismuth subsalicylate nanoparticles with anaerobic antibacterial activity for dental applications,†Nanotechnology, vol. 28, no. 43, 2017.

S. Jain, B. Ch, J. A. Coulter, D. Ph, A. R. Hounsell, and T. Karl, “Cell-Specific Radiosensitization by Gold Nanoparticles at egavoltage Radiation Energies,†Int J Radiat Oncol Biol Phys., vol. 79, no. 2, pp. 531–539, 2011.

W. N. W. A. Rahman, R. A. Rashid, M. Muhammad, N. Dollah, K. A. Razak, and M. Geso, “Dose Enhancement by Different Size of Gold Nanoparticles Under Irradiation of Megavoltage Photon Beam,†J. Sains Nukl. Malaysia, vol. 30, no. 2, pp. 23–29, 2018.

C. Yang, K. Bromma, W. Sung, J. Schuemann, and D. Chithrani, “Determining the radiation enhancement effects of gold nanoparticles in cells in a combined treatment with cisplatin and radiation at therapeutic megavoltage energies,†Cancers (Basel)., vol. 10, no. 150, pp. 1–16, 2018.

E. Shahhoseini, P. Ramachandran, W. R. Patterson, and M. Geso, “Determination of dose enhancement caused by AuNPs with Xoft ® Axxent ® Electronic ( eBx TM ) and conventional brachytherapy : in vitro study,†Int. J. Nanomedicine, vol. 2018, no. 13, pp. 5733–5741, 2018.

S. J. Seo, S. M. Han, J. H. Cho, K. Hyodo, A. Zaboronok, H. You, K. Peach, M. A. Hill, J. K. Kim, “Enhanced production of reactive oxygen species by gadolinium oxide nanoparticles under core–inner-shell excitation by proton or monochromatic X-ray irradiation: implication of the contribution from the interatomic de-excitation-mediated nanoradiator effec,†Radiat. Environ. Biophys., vol. 54, no. 4, pp. 423–431, 2015.

R. M. Lazim, R. A. Rashid, B. T. T. Pham, B. S. Hawkett, M. Geso, and W. N. Rahman, “Radiation Dose Enhancement Effects of Superparamagnetic Iron Oxide nanoparticles to the T24 Bladder Cancer Cell Lines Irradiated with Megavoltage Photon Beam Radiotheray,†J. Sains Nukl. Malaysia, vol. 30, no. 2, pp. 30–38, 2018.

M. Algethami, B. Feltis, and M. Geso, “Bismuth Sulfide Nanoparticles as a Complement to Traditional Iodinated Contrast Agents at Various X-Ray Computed Tomography Tube Potentials,†J. Nanomater. Mol. Nanotechnol., vol. 06, no. 04, pp. 2–10, 2017.

S. Tamilvanan, G. Gurumoorthy, S. Thirumaran, and S. Ciattini, “Synthesis, characterization, cytotoxicity and antimicrobial studies on Bi(III) dithiocarbamate complexes containing furfuryl group and their use for the preparation of Bi2O3nanoparticles,†Polyhedron, vol. 121, pp. 70–79, 2017.

V.A. Ovsyannikov, M.V. Zamoryanskaya, A.V. Semencha, K.A. Lycheva, T.S. Kol’tsova, O.V. Tolochko, and L.N. Blinov, “Development of bismuth oxide-based nanopreparation for the destruction of malignant neoplasms: Theoretical prerequisites, challenges, and practical approaches,†Glas. Phys. Chem., vol. 41, no. 5, pp. 533–536, 2015.

C. Stewart, K. Konstantinov, S. McKinnon, S. Guatelli, M. Lerch, A. Rosenfeld, M. Tehei and S. Corde, “First proof of bismuth oxide nanoparticles as efficient radiosensitisers on highly radioresistant cancer cells,†Phys. Medica, vol. 32, no. 11, 2016.

M. Abudayyak, E. Öztaş, M. Arici, and G. Özhan, “Investigation of the toxicity of bismuth oxide nanoparticles in various cell lines,†Chemosphere, vol. 169, pp. 117–123, 2017.

N. A. M. Nor, Z. Mohd, H. R. A. Razak, Z. Eshak, and W. M. M. Saad, “Synthetisation temperature-dependent cytotoxicity of bismuth oxide nanoparticles in vitro,†Pertanika J. Sci. Technol., vol. 25, no. S, pp. 227–236, 2017.

C. A. C. Stewart, “An investigation into the tailoring of bismuth oxide nanoceramic with a biomedical application as a high Z radiation enhancer for cancer therapy,†University of Wollongong, 2014.

M. Alqathami, A. Blencowe, M. Geso, and G. Ibbott, “Quantitative 3D determination of radiosensitization by bismuth-based nanoparticles,†J. Biomed. Nanotechnol., vol. 12, no. 3, pp. 464–471, 2016.

E. Taha, F. Djouider, and E. Banoqitah, “Monte Carlo simulations for dose enhancement in cancer treatment using bismuth oxide nanoparticles implanted in brain soft tissue,†Australas. Phys. Eng. Sci. Med., vol. 41, pp. 363–370, 2018.

S. Bancos, D. L. Stevens, and K. M. Tyner, “Effect of silica and gold nanoparticles on macrophage proliferation, activation markers, cytokine production, and phagocytosis in vitro,†Int. J. Nanomedicine, vol. 10, pp. 183–206, 2015.

C. Boyoglu, Q. He, G. Willing, S. Boyoglu-Barnum, V. A. Dennis, S. Pillai, and S. R. Singh, “Microscopic Studies of Various Sizes of Gold Nanoparticles and Their Cellular Localizations,†ISRN Nanotechnol., vol. 2013, pp. 1–13, 2013.

T. H. Kim, M. Kim, H. S. Park, U. S. Shin, M. S. Gong, and H. W. Kim, “Size-dependent cellular toxicity of silver nanoparticles,†J. Biomed. Mater. Res. - Part A, vol. 100A, pp. 1033–1043, 2012.

Z. A. Zulkifli, K. A. Razak, and W. N. W. A. Rahman, “The effect of reaction temperature on the particle size of bismuth oxide nanoparticles synthesized via hydrothermal method,†AIP Conf. Proc. 1901, vol. 020007, pp. 1–5, 2018.

Z. A. Zulkifli, K. A. Razak, W. N. W. A. Rahman, and S. Z. Abidin, “Synthesis and Characterisation of Bismuth Oxide Nanoparticles using Hydrothermal Method: The Effect of Reactant Concentrations and application in radiotherapy,†J. Phys. Conf. Ser., vol. 1082, no. 1, 2018.

Y. Li, X. Tian, Z. Lu, C. Yang, G. Yang, X. Zhou, H. Yao, Z. Zhu, Z. Xi and X. Yang, “Mechanism for α-MnO2 Nanowire-Induced Cytotoxicity in Hela Cells,†J. Nanosci. Nanotechnol., vol. 10, no. 1, pp. 397–404, 2010.

Y. Ibuki and T. Toyooka, “Nanoparticle Uptake Measured by Flow Cytometry,†in Nanotoxicity Methods and Protocols, J. Reineke, Ed. Humana Press, 2012.

C. Hanley, A. Thurber, C. Hanna, A. Punnoose, J. Zhang, and D. G. Wingett, “The influences of cell Type and ZnO nanoparticle size on immune cell cytotoxicity and cytokine induction,†Nanoscale Res. Lett., vol. 4, no. 12, pp. 1409–1420, 2009.

D. Hernandez-Patlan, B. Solis-Cruz, A. Mendez-Albores, J. D. Latorre, X. Hernandez-Velasco, G. Tellez, and R. Lopez-Arellano, “Comparison of PrestoBlue ® and plating method to evaluate antimicrobial activity of ascorbic acid, boric acid and curcumin in an in vitro gastrointestinal model,†J. Appl. Microbiol., vol. 124, no. 2, pp. 423–430, 2018.

M. Xu, D. J. McCanna, and J. G. Sivak, “Use of the viability reagent PrestoBlue in comparison with alamarBlue and MTT to assess the viability of human corneal epithelial cells,†J. Pharmacol. Toxicol. Methods, vol. 71, pp. 1–7, 2015.

S. Gaucher and M. Jarraya, “Technical note: comparison of the PrestoBlue and LDH release assays with the MTT assay for skin viability assessment,†Cell Tissue Bank., vol. 16, no. 3, pp. 325–329, 2015.

M. Boncler, M. Rózalski, U. Krajewska, A. Podswdek, and C. Watala, “Comparison of PrestoBlue and MTT assays of cellular viability in the assessment of anti-proliferative effects of plant extracts on human endothelial cells,†J. Pharmacol. Toxicol. Methods, vol. 69, no. 1, pp. 9–16, 2014.

M. Sonnaert, I. Papantoniou, F. P. Luyten, and J. Schrooten, “Quantitative Validation of the Presto BlueTM Metabolic Assay for Online Monitoring of Cell Proliferation in a 3D Perfusion Bioreactor System,†Tissue Eng. Part C Methods, vol. 21, no. 6, pp. 519–529, 2014.

C. Zhu, W. Hu, H. Wu, and X. Hu, “No evident dose-response relationship between cellular ROS level and its cytotoxicity - A paradoxical issue in ROS-based cancer therapy,†Sci. Rep., vol. 4, no. 5029, pp. 1–10, 2014.

V. Jamier, L. A. Ba, and C. Jacob, “Selenium- and tellurium-containing multifunctional redox agents as biochemical redox modulators with selective cytotoxicity,†Chem. - A Eur. J., vol. 16, no. 36, pp. 10920–10928, 2010.

E. L. H. Tang, J. Rajarajeswaran, S. Y. Fung, and M. S. Kanthimathi, “Antioxidant Activity of Coriandrum sativum and Protection Against DNA Damage and Cancer Cell Migration,†BMC Complement. Altern. Med., vol. 13, no. 347, pp. 1–13, 2013.

L. Tong, C. Chuang, S. Wu, and L. Zuo, “Reactive oxygen species in redox cancer therapy,†Cancer Lett., vol. 07, no. 008, 2015.

M. V. D. Z. Park, A. M. Neigh, J. P. Vermeulen, L. J. J. de la Fonteyne, H. W. Verharen, J. J. Briede, H. van Loveren, and W. H. de Jong, “The effect of particle size on the cytotoxicity, inflammation, developmental toxicity and genotoxicity of silver nanoparticles,†Biomaterials, vol. 32, no. 36, pp. 9810–9817, 2011.

H. Turkez and F. Geyikoglu, “The efficiacy of bismuth subnitrate against genotoxicity and oxidative stress induced by aluminum sulphate,†Toxicol. Ind. Health, vol. 27, no. 2, pp. 133–142, 2011.

M. Ahamed, M. J. Akhtar, M. A. M. Khan, S. A. Alrokayan, and H. A. Alhadlaq, “Oxidative stress mediated cytotoxicity and apoptosis response of bismuth oxide (Bi2O3) nanoparticles in human breast cancer (MCF-7) cells,†Chemosphere, vol. 216, pp. 823–831, 2019.

A. Salvati, I. Nellissen, A. Hasae, C. Aberg, S. Moya, A. Jacobs, F. Alnasser, T. Bewersdorff, S. Deville, A. Luch, and K. A. Dawson, “Quantitative measurement of nanoparticle uptake by flow cytometry illustrated by an interlaboratory comparison of the uptake of labelled polystyrene nanoparticles,†NanoImpact, vol. 9, no. September 2017, pp. 42–50, 2018.

A. Jochums, E. Friehs, F. Sambale, A. Lavrentieva, D. Bahnemann, and T. Scheper, “Revelation of Different Nanoparticle-Uptake Behavior in Two Standard Cell Lines NIH/3T3 and A549 by Flow Cytometry and Time-Lapse Imaging,†Toxics, vol. 5, no. 3, p. 15, 2017.

H. Yang, Q. Y. Wu, C.S. Lao, M. Y. Li, Y. Gao, Y. Zheng, and B. Shi, “Cytotoxicity and DNA damage in mouse macrophages exposed to silica nanoparticles,†Genet. Mol. Res., vol. 15, no. 3, pp. 1–14, 2016.

I. L. Hsiao, F. S. Bierkandt, P. Reichardt, A. Luch, Y-J. Huang, N. Jakubowski, J. Tentschert, and A. Haase, “Quantification and visualization of cellular uptake of TiO2 and Ag nanoparticles: Comparison of different ICP-MS techniques,†J. Nanobiotechnology, vol. 14, no. 1, pp. 1–13, 2016.

B. D. Chithrani, A. A. Ghazani, and W. C. W. Chan, “Determining the Size and Shape Dependence of Gold Nanoparticles Uptake Into Mammalian Cells,†Nano Lett., vol. 6, no. 4, pp. 662–668, 2006.

P. V Asharani, N. Xinyi, M. P. Hande, and S. Valiyaveettil, “DNA damage and p53-mediated growth arrest in human cells treated with platinum nanoparticles.†Nanomedicine, vol. 5, no. 1, pp. 51–64, 2010.

R. A. Rashid, N. Dollah, R. Abdullah, and W. N. W. A. Rahman, “The effects of wound dressings on the dose at surface and depth of maximum dose (dmax) for photon and electron beam radiotherapy,†J. Med. Phys. Biophys., vol. 4, no. 1, pp. 103–107, 2017.

W. N. W. A. Rahman, “Gold nanoparticles: novel radiobiological dose enhancement studies for radiation therapy, synchrotron based microbeam and stereotactic radiotherapy,†RMIT University, 2010.

J. C. L. Chow, “Photon and electron interactions with gold nanoparticles: A Monte Carlo study on gold nanoparticle-enhanced radiotherapy,†in Nanobiomaterials in Medical Imaging: Applications of Nanobiomaterials, Elsevier Inc., 2016, pp. 45–70.

A. Detappe, S. Kunjachan, P. Drane, S. Kotb, M. Myronakis, D. E. Biancur, T. Ireland, M. Wagar, F. Lux, O. Tillement, and R. Berbeco, “Key clinical beam parameters for nanoparticle-mediated radiation dose amplification,†Nat. Sci. Reports, vol. 6, no. 34040, pp. 1–8, 2016.




DOI: http://dx.doi.org/10.18517/ijaseit.9.4.7218

Refbacks

  • There are currently no refbacks.



Published by INSIGHT - Indonesian Society for Knowledge and Human Development