open j. nano Open Journal of Nano 2147-0081 Mustafa CAN 10.56171/ojn.1189800 Nanopartiküllerin Toksikolojik Yönleri ve Biyo-Analizleri: Zebra Balığı Modeli Toxicological Aspects and Bioanalysis of Nanoparticles: Zebrafish Model https://orcid.org/0000-0002-3627-0024 Yeşilbudak Burcu ÇUKUROVA ÜNİVERSİTESİ 06 30 2023 8 1 22 35 10 15 2022 11 29 2022 Copyright © 2012, Open Journal of Nano 2012 Open Journal of Nano

Nanopartiküller, dünya coğrafyasının doğal oluşum süreçleri ve ileri teknolojik sanayinin gelişimi ile çevredeki bulunurluklarını ve çeşitliliğini her geçen gün arttırmaktadır. Akıllı ve sürekli değişen fiziko-kimyasal yapısal formları nedeniyle organizmada çeşitli metabolik basamaklarda (yapı proteinlerinde, genetik yapıda, organellerde, hücrede, dokuda, organlarda, metabolik sistemlerde) toksik etkilere neden olabilmektedirler. Bu zararlı durumlara karşın altın nanopartiküller, gümüş nanopartiküller, nanoelmaslar, dendrimerler, polimerik ve lipozomik akıllı nanopartiküller gibi bazı manyetit nanopartiküller medikal çalışmalarda, eczacılık endüstrisinde, nanoteranostik çalışmalarda ve moleküler yöntemlerde kullanılabilmektedir. Birçok çalışma disiplininde model tür olarak kullanılan zebra balığı (Danio rerio) test edilen nanopartiküllerin potansiyel toksik etkileri ile pozitif etkilerini ortaya çıkarmak için bir çok çalışmada kullanılmıştır. Halihazırdaki bu çalışmayla son yıllardaki hem in vivo hem de in vitro test sistemleri ile interdisipliner boyutlu çalışmalar geleneksel derleme yöntemiyle araştırılmış ve değerlendirilmiştir. Ayrıca nanopartiküllerin karakterizasyonları ile etki mekanizmalarını anlamak konusunda hızlı ve verimli sonuçlar almak için birçok çalışma gruplandırılmıştır. Mayıs 2022'de PubMed, Google Scholar, Web of Science ve Carrot² gibi veri tabanlarında bu çalışmanın anahtar kelimeleri baz alınarak sistematik bir tarama yapıldı. Nanopartiküllerin toksik etkilerinin anlaşılmasının yanı sıra medikal, eczacılık, moleküler ve genetik uygulamalı çalışmalarda nanopartiküllerin faydacı durumlarının her geçen gün daha da anlaşıldığı çeşitli çalışmalar vurgulanmıştır.

Nanoparticles increase their availability and diversity in the environment day by day with the natural formation processes of the world geography and the development of advanced technological industry. Due to their intelligent and kaleidoscopic physico-chemical structural forms, they can cause toxic effects in various metabolic steps (in structural proteins, genetic structure, organelles, cells, tissues, organs, metabolic systems) in the organism. Despite these harmful situations some magnetite nanoparticles such as gold nanoparticles, silver nanoparticles, nanodiamonds, dendrimers, polymeric and liposomic smart nanoparticles can be used in medical studies, pharmaceutical industry, nanotheranostic studies and molecular methods. Zebrafish (Danio rerio), which is used a model species in many study disciplines, has been used in many studies to reveal the potential toxic effects and positive effects of the tested nanoparticles. Both in vivo and in vitro test systems and interdisciplinary studies conducted in recent years were analyzed and evaluated via the traditional review method in the current study. Besides, many studies were grouped in order to obtain fast and efficient results on the characterization of nanoparticles and understanding their mechanism of action. A systematic search was conducted based on the keywords of this study in databases such as PubMed, Google Scholar, Web of Science and Carrot², in May 2022. In addition to recognizing the toxic effects of nanoparticles, several studies were emphasized, in which the utilitarian status of nanoparticles in medical, pharmaceutical, molecular and genetic applied studies was understood more clearly day by day.

 Nanoparticle Toxic Zebrafish Model species Nanopartikül Toksik Zebra balığı Model tür [1] Kroll, A., Pillukat, M. H., Hahn, D., and Schnekenburger, J. (2009). Current in vitro methods in nanoparticle risk assessment: limitations and challenges. Euro. J. Pharmaceutic. Biopharmac., 72(2), 370-377. DOI:10.1016/j.ejpb.2008.08.009. [2] Gong P, Li H, He X, Wang K, Hu J, and Tan W. (2007). Preparation and antibacterial activity of Fe3O4@ Ag nanoparticles. Nanotech., 18(28), 285604. [3] Jiang, J., Pi, J., and Cai, J. (2018). The advancing of zinc oxide nanoparticles for biomedical applications. Bioinorganic Chemistry and Applications, 1-18. DOI:10.1155/2018/1062562. [4] Asmatulu, R., Nguyen, P., and Asmatulu, E. (2013). Nanotechnology safety in the automotive industry. In Nanotech. Elsevier, Amsterdam, pp 57-72. DOI:10.1016/B978-0-444-59438-9.00005-9. [5] Buzea, C., Pacheco, I., and Robbie, K. (2007). Nanomaterials and nanoparticles: sources and toxicity. Biointerphases, 2(4), Mr17-Mr71. DOI:10.1116/1.2815690 [6] Rizwan, M., Shoukat, A., Ayub, A., Razzaq, B., and Tahir, M.B. (2021). Types and classification of nanomaterials. In Nanomaterials: Synthesis, Characterization, Hazards and Safety. Elsevier, Amsterdam, pp. 31-54. [7] Domingos, R.F., Tufenkji, N., and Wilkinson, K.J. (2009). Aggregation of titanium dioxide nanoparticles: role of a fulvic acid. Environ. Sci. Tech., 43(5),1282-1286. DOI: 10.1021/es8023594. [8] Daughton, C.G. (2004). Non-regulated water contaminants: Emerging research. Environment. Impact. Assess. Rev., 24, 711-732. DOI: 10.1016/j.eiar.2004.06.003. [9] Asztemborska, M., Jakubiak, M., Książyk, M., Stęborowski, R., Polkowska-Motrenko, H., and Bystrzejewska-Piotrowska, G. (2014). Silver nanoparticle accumulation by aquatic organisms-neutron activation as a tool for the environmental fate of nanoparticles tracing. Nukleonika, 59(4), 169-173. DOI: 10.2478/nuka-2014-0023. [10] Santoriello, C. and Zon, L.I. (2012). Hooked! Modeling human disease in zebrafish. The J. Clinic. Invest., 122(7), 2337-2343. DOI:10.1172/JCI60434. [11] Zhao, S., Huang, J., and Ye, J. (2015). A fresh look at zebrafish from the perspective of cancer research. J. Experiment. Clinic. Cancer. Res., 34(1), 1-9. DOI: 10.1186/s13046-015-0196-8. [12] Patel, K.D., Singh, R.K., and Kim, H.W. (2019). Carbon-based nanomaterials as an emerging platform for theranostics. Mater. Horiz., 6(3), 434-469. DOI:10.1039/c8mh00966j. [13] Radomski, A., Jurasz, P., Alonso-Escolano, D., Drews, M., Morandi, M., Malinski, T., and Radomski, M.W. (2005). Nanoparticle-induced platelet aggregation and vascular thrombosis. Br. J. Pharmacol., 146, 882-893. DOI:10.1038/sj.bjp.0706386. [14] Mengesha, A.E. and Youan, B.B.C. (2013). Nanodiamonds for drug delivery systems. In Diamond-based materials for biomedical applications. Woodhead Publishing, Cambridge, pp. 186-205. DOI:10.1533/9780857093516.2.186. [15] Aschberger, K., Johnston, H., Stone, V., Aitken, R., Tran, C., Hankin, S., Peters, S., and Christensen, F. (2010). Review of fullerene toxicity and exposure-appraisal of a human health risk assessment, based on open literature. Regul. Toxicol. Pharmacol., 58(3), 455-473. DOI:10.1016/j.yrtph.2010.08.017. [16] Ming, Z., Feng, S., Yilihamu, A., Ma, Q., Yang, S., and Yang, S. T. (2018). Toxicity of pristine and chemically functionalized fullerenes to white rot fungus Phanerochaete chrysosporium. Nanomat., 8(2), 120. DOI:doi.org/10.3390/nano8020120. [17] Asmatulu, E., Andalib, M.N., Subeshan, B., and Abedin, F. (2022). Impact of nanomaterials on human health: a review. Environ. Chem. Let., 1-21. [18] Jia, Y.P, Ma, B.Y., Wei, X.W., and Qian, Z.Y., (2017). The in vitro and in vivo toxicity of gold nanoparticles. Chin. Chem. Lett., 28(4), 691-702. DOI:10.1016/j.cclet.2017.01.021. [19] Papageorgiou, I., Brown, C., Schins, R., Singh, S., Newson, R., and Davis, S. (2007). The effect of nano- and micron-sized particles of cobalt-chromium alloy on human fibroblasts in vitro. Biomat., 28(19), 2946-2958. DOI:10.1016/j.biomaterials.2007.02.034. [20] Cameron, S.J., Hosseinian, F., Willmore, W.G. (2018). A current overview of the biological and cellular efects of nanosilver. Int. J. Mol. Sci., 19(7), 2030. DOI:10.3390/ijms19072030. [21] Chen, L.Q., Fang, L., Ling, J., Ding, C.Z., Kang, B., and Huang, C.Z. (2015). Nanotoxicity of silver nanoparticles to red blood cells: size dependent adsorption, uptake, and hemolytic activity. Chem. Res. Toxicol., 28(3), 501-509. DOI:10.1021/tx500479m. [22] Guo, Z., Zeng, G., Cui, K., Chen, A. (2019). Toxicity of environmental nanosilver: mechanism and assessment. Environ. Chem Lett. 17(1), 319-333. DOI:10.1007/s10311-018-0800-1. [23] Pulit-Prociak, J., Stokłosa, K., and Banach, M. (2014). Nanosilver products and toxicity. Environ. Chem. Lett., 13(1), 59-68. DOI:10.1007/s10311-014-0490-2. [24] Radzium, E., Wilczyńska, J.D., Książek, I., Nowak, K., Anuszewska, E.L., Kunicki, A., Olszyna, A., and Ząbkowski, T. (2011). Assessment of the cytotoxicity of aluminum oxide nanoparticles on selected mammalian cells. Toxicol. In Vitro, 25, 1694-1700. DOI:10.1016/j.tiv.2011.07.010. [25] Sun, J., Wang, S., Zhao, D., Hun, F.H., Weng, L., and Liu, H. (2011). Cytotoxicity, permeability, and inflammation of metal oxide nanoparticles in human cardiac microvascular endothelial cells: cytotoxicity, permeability, and inflammation of metal oxide nanoparticles. Cell. Biol. Toxicol., 27, 333-342. DOI:10.1007/s10565-011-9191-9. [26] Kumar, V. and Gill, K.D. (2009). Aluminium neurotoxicity: neurobehavioural and oxidative aspects. Archives of toxicology, 83(11), 965-978. DOI:10.1007/s00204-009-0455-6. [27] Alshatwi, A.A., Vaiyapuri Subbarayan, P., Ramesh, E., Al-Hazzani, A.A., Alsaif, M.A., and Alwarthan, A.A. (2012). Al2O3 nanoparticles induce mitochondriamediated cell death and upregulate the expression of signaling genes in human mesenchymal stem cells. J. Biochem. Mol. Toxicol., 26, 469-476. DOI:10.1002/jbt.21448. [28] Zhang, Q.L., Li, M.Q., Ji, J.W., Gao, F.P., Bai, R., Chen, C.Y., Wang, Z.W., Zhang, C., and Niu, Q. (2011). In vivo toxicity of nano-alumina on mice neurobehavioral profiles and the potential mechanisms. Int. J. Immunopathol. Pharmacol. 24(1), 23S-29S. PMID: 21329562. [29] Gao, G., Ze, Y., Zhao, X., Sang, X., Zheng, L., Ze, X., Gui, S., Sheng, L., Sun, Q., Hong, J., Yu, X., Wang, L., and Zhang, F.H. (2013) Titanium dioxide nanoparticle-induced testicular damage, spermatogenesis suppression, and gene expression alterations in male mice. J. Hazard. Mater., 258, 133-143. DOI:10.1016/j.jhazmat.2013.04.046. [30] Gao, J., Liang, G., Zhang, B., Kuang, Y., Zhang, X., and Xu, B. (2007). FePt@CoS(2) yolk-shell nanocrystals as a potent agent to kill HeLa cells. J. Am. Chem. Soc., 129, 1428-1433. DOI:10.1021/ja067785e. [31] Laurent, S., Duts, S., Hafeli, U., and Mahmoudi, M. (2011). Magnetic fluid hyperthermia: Focus on superparamagnetic iron oxide nanoparticles. Adv. Colloid Interface Sci., 166, 8-23. DOI:10.1016/j.cis.2011.04.003. [32] Mahmoudi, M., Hosseinkhani, H., Hosseinkhani, M., Boutry, S., Simchi, A., Journeay, W. S., Subramani, K., and Laurent, S. (2011). Magnetic resonance imaging tracking of stem cells in vivo using iron oxide nanoparticles as a tool for the advancement of clinical regenerative medicine. Chem. Rev., 111, 253-280. DOI:10.1021/cr1001832. [33] Mailander, V., Lorenz, M. R., Holzapfel, V., Musyanovych, A., Fuchs, K., Wiesneth, M., Walther, P., Landfester, K., and Schrezenmeier, H. (2008). Carboxylated superparamagnetic iron oxide particles label cells intracellularly without transfection agents. Mol. Imaging Biol., 10, 138-146. DOI:10.1007/s11307-007-0130-3. [34] Gupta, A. K., Naregalkar, R.R., Vaidya, V.D., and Gupta, M. (2007). Recent advances on surface engineering of magnetic iron oxide nanoparticles and their biomedical applications. Nanomed. 2, 23-39. DOI:10.2217/17435889.2.1.23. [35] Anonymous. (2022). Nanotechnology Now. Retrieved from http://www.nanotech-now.com/2003-Awards. (21.08.2022). [36] Chan, W.C.W., Maxwell, D.J., Gao, X.H., Bailey, R.E., Han, M.Y., and Nie, S.M. (2002). Luminescent quantum dots for multiplexed biological detection and imaging. Curr. Opin. Biotech., 13, 40-6. DOI:10.1016/S0958-1669(02)00282-3. [37] Babu, V.R., Nikhat, M.S.R., and Srikanth, G. (2010). Dendrimers: a new carrier system for drug delivery. Int. J. Pharmaceutic. App.Sci., 1(1), 1-10. [38] Geranio, L., Hommes, G., Shahgaldian,, P., Wirth-Heller, A., Pieles, U., and Corvini, P.F.X. (2010). Radio (14C)-and fuorescent-doubly labeled silica nanoparticles for biological and environmental toxicity assessment. Environ. Chem. Lett., 8(3), 247-251. DOI:10.1007/s10311-009-0213-2. [39] Kim, I.S., Baek, M., and Choi, S-J. (2010). Comparative cytotoxicity of Al2O3, CeO2, TiO2 and ZnO nanoparticles to human lung cells. J. Nanosci. Nanotechnol., 10(5), 3453-3458. DOI:10.1166/ jnn.2010.2340. [40] Duan, J., Yu, Y., Li, Y., Yu, Y., Li, Y., Zhou, X., Huang, P., and Sun, Z. (2013). Toxic efect of silica nanoparticles on endothelial cells through DNA damage response via Chk1-dependent G2/M checkpoint. PLOS ONE 8(4), e62087. DOI:10.1371/journal.pone.0062087. [41] Zhou, F., Liao, F., Chen, L., Liu, Y, Wang, W., and Feng, S. (2019). The sizedependent genotoxicity and oxidative stress of silica nanoparticles on endothelial cells. Environ. Sci. Pollut. Res. Int., 26(2), 1911-1920. DOI:10.1007/s11356-018-3695-2. [42] Li, A., Zhang, C., and Zhang, Y.F. (2017). Thermal conductivity of graphene-polymer composites: Mechanisms, properties, and applications. Polyme, 9(9), 437. DOI:10.3390/polym9090437. [43] Medina, C., Santos-Martinez, M.J., Radomski, A., Corrigan, O.I., and Radomski, M.W. (2007). Nanoparticles: pharmacological and toxicological significance. Br. J. Pharmacol., 150(5), 552-558. DOI:10.1038/sj.bjp.0707130. [44] Kumari, M., Singla, M., Sobti, R.C. (2022). Animal models and their substitutes in biomedical research. In Advances in Animal Experimentation and Modeling. Academic Press, Cambridge, 87-101. DOI:10.1016/B978-0-323-90583-1.00014-3. [45] Chen, D., Zhang, D., Jimmy, C. Y., and Chan, K.M. (2011). Effects of Cu2O nanoparticle and CuCl2 on zebrafish larvae and a liver cell-line. Aquat. Toxicol., 105(3-4), 344-354. DOI:10.1016/j.aquatox.2011.07.005. [46] Choi, J. E., Kim, S., Ahn, J. H., Youn, P., Kang, J. S., Park, K., and Ryu, D.Y. (2010). Induction of oxidative stress and apoptosis by silver nanoparticles in the liver of adult zebrafish. Aquat. Toxicol., 100(2), 151-159. DOI: 10.1016/j.aquatox.2009.12.012. [47] Fent, K., Weisbrod, C. J., Wirth-Heller, A., and Pieles, U. (2010). Assessment of uptake and toxicity of fluorescent silica nanoparticles in zebrafish (Danio rerio) early life stages. Aquat. Toxicol., 100(2), 218-228. DOI: 10.1016/j.aquatox.2010.02.019. [48] Griffitt, R.J., Lavelle, C.M., Kane, A.S., Denslow, N.D., and Barber, D.S. (2013). Chronic nanoparticulate silver exposure results in tissue accumulation and transcriptomic changes in zebrafish. Aquat. Toxicol., 130, 192-200. DOI: 10.1016/j.aquatox.2013.01.010. [49] Kaloyianni, M., Dimitriadi, A., Ovezik, M., Stamkopoulou, D., Feidantsis, K., Kastrinaki, G., Gallios, G., Tsiaoussis, I., Koumoundouros, G., and Bobori, D. (2020). Magnetite nanoparticles effects on adverse responses of aquatic and terrestrial animal models. J. Hazard. Material., 383, 121204. DOI:10.1016/j.jhazmat.2019.121204. [50] Souza, J.P., Baretta, J.F., Santos, F., Paino, I.M., and Zucolotto, V. (2017). Toxicological effects of graphene oxide on adult zebrafish (Danio rerio). Aquat. Toxicol., 186, 11-18. DOI: 10.1016/j.aquatox.2017.02.017. [51] Weber, G.E., Dal Bosco, L., Gonçalves, C.O., Santos, A.P., Fantini, C., Furtado, C.A. and Barros, D.M. (2014). Biodistribution and toxicological study of PEGylated single-wall carbon nanotubes in the zebrafish (Danio rerio) nervous system. Toxicol. App. Pharmacol., 280(3), 484-492. DOI: 10.1016/j.taap.2014.08.018. [52] Xiong, D., Fang, T., Yu, L., Sima, X., and Zhu, W. (2011). Effects of nano-scale TiO2, ZnO and their bulk counterparts on zebrafish: acute toxicity, oxidative stress and oxidative damage. Sci. Total Environ., 409, 1444-1452. DOI:10.1016/j.scitotenv. 2011.01.015. [53] Zhu, X., Tian, S., and Cai, Z. (2012). Toxicity assessment of iron oxide nanoparticles in zebrafish (Danio rerio) early life stages. PLoS One 7(9), e46286. DOI:10. 1371/journal.pone.0046286. [54] Holtzman, N. G., Iovine, M. K., Liang, J. O., and Morris, J. (2016). Learning to fish with genetics: a primer on the vertebrate model Danio rerio. Genetics, 203(3), 1069-1089. DOI: 10.1534/genetics.116.190843 . [55] Blanco-Vives, B., and Sanchez-Vazquez, F. J. (2009). Synchronisation to light and feeding time of circadian rhythms of spawning and locomotor activity in zebrafish. Physiol. Behav., 98, 268-275. DOI: 10.1016/j.physbeh.2009.05.015 . [56] Wang, X. and Wang, W.X. (2022). Cu-based nanoparticle toxicity to zebrafish cells regulated by cellular discharges. Environ. Pollut., 292, 118296. DOI:10.1016/j.envpol.2021.118296. [57] Shi, L., Li, Y., Zhang, S., Gong, X., Xu, J., and Guo, Y. (2022). Construction of inulin-based selenium nanoparticles to improve the antitumor activity of an inulin-type fructan from chicory. Int. J. Biol. Macromolecul., 210, 261-270. DOI:10.1016/j.ijbiomac.2022.04.125. [58] Igartúa, D.E., Azcona, P. L., Martinez, C.S., del Valle Alonso, S., Lassalle, V. L., and Prieto, M.J. (2018). Folic acid magnetic nanotheranostics for delivering doxorubicin: toxicological and biocompatibility studies on Zebrafish embryo and larvae. Toxicol. App. Pharmacol., 358, 23-34. DOI:10.1016/j.taap.2018.09.009. [59] Nellore, J., Pauline, C., and Amarnath, K. (2013). Bacopa monnieri phytochemicals mediated synthesis of platinum nanoparticles and its neurorescue effect on 1-methyl 4-phenyl 1, 2, 3, 6 tetrahydropyridine-induced experimental parkinsonism in zebrafish. J. Neurodegener. Dis., 2013, 1-8. DOI:10.1155/2013/972391. [60] Chen, P.J., Wu, W.L., and Wu, K.C.W. (2013). The zerovalent iron nanoparticle causes higher developmental toxicity than its oxidation products in early life stages of medaka fish. Wat. Res., 47(12), 3899-3909. DOI:10.1016/j.watres.2012.12.043. [61] Zhu, X., Wang, J., Zhang, X., Chang, Y., and Chen, Y. (2010). Trophic transfer of TiO2 nanoparticles from daphnia to zebrafish in a simplified freshwater food chain. Chemosph., 79(9), 928-933. DOI: 10.1016/j.chemosphere.2010.03.022. [62] Skjolding, L.M., Winther-Nielsen, M., and Baun, A. (2014). Trophic transfer of differently functionalized zinc oxide nanoparticles from crustaceans (Daphnia magna) to zebrafish (Danio rerio). Aquat. Toxicol., 157, 101-108. DOI:10.1016/j.aquatox.2014.10.005. [63] Boxall, A.B.A., Chaundhry, Q., Sinclair, C., Jones, A., Aitken, R., Jefferson, B., and Watts, C. (2007). Current and future predicted environmental exposure to engineered nanoparticles. Report by the Central Science Laboratory (CSL) York for the Department of the Environment and Rural Affairs (DEFRA), UK, pp. 89. [64] Al-Thani, H. F., Shurbaji, S., Zakaria, Z. Z., Hasan, M. H., Goracinova, K., Korashy, H. M., and Yalcin, H.C. (2022). Reduced Cardiotoxicity of Ponatinib-Loaded PLGA-PEG-PLGA Nanoparticles in Zebrafish Xenograft Model. Material., 15(11), 3960. DOI:10.3390/ma15113960. [65] Yu, F., Xiang, H., He, S., Zhao, G., Cao, Z., Yang, L., and Liu, H. (2022). Gold nanocluster-based ratiometric fluorescent probe for biosensing of Hg2+ ions in living organisms. Analyst. 147, 2773-2778. DOI:10.1039/D2AN00369D. [66] Nie, H., Pan, M., Chen, J., Yang, Q., Hung, T.C., Xing, D., Peng, M., Peng, X., Li, G., and Yan, W. (2022). Titanium dioxide nanoparticles decreases bioconcentration of azoxystrobin in zebrafish larvae leading to the alleviation of cardiotoxicity. Chemosph., 307, 135977. DOI:10.1016/j.chemosphere.2022.135977.