Abstract
In order to evaluate the biodistribution and toxicity of europium-doped Gd2O3 nanotubes, we synthesized Gd2O3:Eu3+ nanotubes via a simple wet-chemical route at ambient pressure. The as-obtained Gd2O3:Eu3+ sample is composed of uniform and well-dispersed nanotubes. The diameters and lengths of the nanotubes are about 50 and 300 nm, respectively. All mice of the experimental groups were administered by intraperitoneal injection everyday over a period of 60 days at doses ranging from 1.25 to 125 mg/kg. Haematological and biochemical parameters and histopathology were examined, and the biodistribution of Gd element in different organs was analyzed. The results indicate that the spleen shows significant higher coefficient than the control, and other organs have no obvious difference from the control in the middle-dose and high-dose groups. There was no significant difference in the blood-elements between the control group and the experimental groups, and no significant change of all parameters can be observed in both low-dose and middle-dose groups. However, in the high-dose group, the ALT, AST, the ratio of AST/ALT, UA, LDH, and HBDH levels was increased significantly in comparison with the control group. The pathology results show that the ischemia of myocardial cell, hemorrhage of lung tissue, hepatocyte necrosis, congestion of renal interstitium, mesangial cell proliferation, and congestion of spleen sinus were induced by high-dose Gd2O3:Eu3+ nanotubes. Biodistribution experiment exhibits that Gd mainly accumulates in spleen, lung, and liver. Therefore, it can be concluded that high-dose Gd2O3:Eu3+ nanotubes were toxic, but low-dose and middle-dose groups did not show significant toxicity. The results provide novel toxicology data of Gd2O3:Eu3+ nanotubes and may be helpful for more rational applications of Gd-based compounds in the future.
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References
Abraham JL, Thakral C, Skov L, Rossen K, Marckmann P (2008) Dermal inorganic gadolinium concentrations: evidence for in vivo transmetallation and long-term persistence in nephrogenic systemic fibrosis. Br J Dermatol 158:273–280
Aillon KL, Xie Y, El-Gendy N, Berkland CJ, Forrest ML (2009) Effects of nanomaterial physicochemical properties on in vivo toxicity. Adv Drug Deliv Rev 61:457–466
Chen C, Xing G, Wang J, Zhao Y, Li B, Tang J, Jia G, Wang T, Sun J, Xing L, Yuan H, Gao Y, Meng H, Chen Z, Zhao F, Chai Z, Fang X (2005) Multihydroxylated [Gd@C82(OH)22]n nanoparticles: antineoplastic activity of high efficiency and low toxicity. Nano Lett 5:2050–2057
Cowper SE, Rabach M, Girardi M (2008) Clinical and histological findings in nephrogenic systemic fibrosis. Eur J Radiol 66:191–199
Fischer HC, Chan WC (2007) Nanotoxicity: the growing need for in vivo study. Curr Opin Biotechnol 18:565–571
Hemmer E, Takeshita H, Yamano T, Fujiki T, Kohl Y, Löw K, Venkatachalam N, Hyodo H, Kishimoto H, Soga K (2012) In vitro and in vivo investigations of upconversion and NIR emitting Gd2O3:Er3+, Yb3+ nanostructures for biomedical applications. J Mater Sci Mater Med 23:2399–2412
Hirst SM, Karakoti A, Singh S, Self W, Tyler R, Seal S, Reilly CM (2013) Bio-distribution and in vivo antioxidant effects of cerium oxide nanoparticles in mice. Environ Toxicol 28:107–118
Idée JM, Port M, Raynal I, Schaefer M, Le Greneur S, Corot C (2006) Clinical and biological consequences of transmetallation induced by contrast agents for magnetic resonance imaging: a review. Fundam Clin Pharmacol 20:563–576
Jia G, Liu K, Zheng Y, Song Y, Yang M, You H (2009) Highly uniform Gd(OH)3 and Gd2O3:Eu3+ nanotubes: facile synthesis and luminescence properties. J Phys Chem C 113:6050–6055
Krug HF, Wick P (2011) Nanotoxicology: an interdisciplinary challenge. Anqew Chem Int Ed Enql 50:1260–1278
Le UM, Cui Z (2006) Long-circulating gadolinium-encapsulated liposomes for potential application in tumor neutron capture therapy. Int J Pharm 312:105–112
Magda D, Miller RA (2006) Motexafin gadolinium: a novel redox active drug for cancer therapy. Semin Cancer Biol 16:466–476
Nakamura Y, Tsumura Y, Tonoqai Y, Shibata T, Ito Y (1997) Differences in behavior among the chlorides of seven rare earth elements administered intravenously to rats. Fundam Appl Toxicol 37:106–116
Palasz A, Czekaj P (2000) Toxicological and cytophysiological aspects of lanthanides action. Acta Biochim Pol 47:1107–1114
Patra CR, Abdel Moneim SS, Wang E, Dutta S, Patra S, Eshed M, Mukherjee P, Gedanken A, Shah VH, Mukhopadhyay D (2009) In vivo toxicity studies of europium hydroxide nanorods in mice. Toxicol Appl Pharmacol 240:88–98
Pradhan AK, Zhang K, Bahoura M, Pradhan J, Ravichandran P, Gopikrishnan R, Ramesh GT (2011) Synthesis, characterization, toxicity of nanomaterials for biomedical applications. In: Anthony L (ed) Biomedical engineering, trends in materials science. Intech, Rijeka, pp 348–374
Rada S, Rada M, Culea E (2011) Structural and optical properties of the gadolinium–lead–germanate glasses. J Non-Cryst Solids 357:62–66
Radford IR (2000) Gd-Tex Pharmacyclics Inc. Curr Opin Investiq Drugs 1:524–528
Samet JM, Dominici F, Curriero FC, Coursac I, Zeger SL (2000) Fine particulate air pollution and mortality in 20 U.S. cities, 1987–1994. N Engl J Med 343:1742–1749
Sarkar A, Das J, Manna P, Sil PC (2011) Nano-copper induces oxidative stress and apoptosis in kidney via both extrinsic and intrinsic pathways. Toxicology 290:208–217
Sessler JL, Miller RA (2000) Texaphyrins: new drugs with diverse clinical applications in radiation and photodynamic therapy. Biochem Pharmacol 59:733–739
Sharma P, Brown SC, Walter G, Santra S, Scott E, Ichiwaka H, Fukumori Y, Moudgil BM (2007) Gd nanoparticulates: from magnetic resonance imaging to neutron capture therapy. Adv Powder Technol 18:663–698
Sherry AD, Caravan P, Lenkinski RE (2009) Primer on gadolinium chemistry. J Magn Reson Imaging 30:1240–1248
Sung JH, Ji JH, Park JD, Yoon JU, Kim DS, Jeon KS, Song MY, Jeong J, Han BS, Han JH, Chung YH, Chang HK, Lee JH, Cho MH, Kelman BJ, Yu IJ (2009) Subchronic inhalation toxicity of silver nanoparticles. Toxicol Sci 108:452–461
Thomsen HS (2004) Gadolinium-based contrast media may be nephrotoxic even at approved doses. Eur Radiol 14:1654–1656
Von Klot S, Wolke G, Tuch T, Heinrich J, Dockery DW, Schwartz J, Kreyling WG, Wichmann HE, Peters A (2002) Increased asthma medication use in association with ambient fine and ultrafine particles. Eur Respir J 20:691–702
Wang H, Wang J, Deng X, Sun H, Shi Z, Gu Z, Liu Y, Zhao Y (2004) Biodistribution of carbon single-wall carbon nanotubes in mice. J Nanosci Nanotechnol 4:1019–1024
Wang B, Feng WY, Wang TC, Jia G, Wang M, Shi JW, Zhang F, Zhao YL, Chai ZF (2005) Acute toxicity of nano- and micro-scale zinc powder in healthy adult mice. Toxicol Lett 161:115–123
Wang J, Chen C, Li B, Yu H, Zhao Y, Sun J, Li Y, Xing G, Yuan H, Tang J, Chen Z, Meng H, Gao Y, Ye C, Chai Z, Zhu C, Ma B, Fang X, Wan L (2006) Antioxidative function and biodistribution of [Gd@C82(OH)22]n nanoparticles in tumor-bearing mice. Biochem Pharmacol 71:872–881
Wang J, Zhou G, Chen C, Yu H, Wang T, Ma Y, Jia G, Gao Y, Li B, Sun J, Li Y, Jiao F, Zhao Y, Chai Z (2007) Acute toxicity and biodistribution of different sized titanium dioxide particles in mice after oral administration. Toxicol Lett 168:176–185
Wang B, Feng W, Wang M, Wang T, Gu Y, Zhu M, Ouyang H, Shi J, Zhang F, Zhao Y, Chai Z, Wang H, Wang J (2008) Acute toxicological impact of nano- and submicro-scaled zinc oxide powder on healthy adult mice. J Nanopart Res 10:263–276
Yokel RA, Au TC, MacPhail R, Hardas SS, Butterfield DA, Sultana R, Goodman M, Tseng MT, Dan M, Haghnazar H, Unrine JM, Graham UM, Wu P, Grulke EA (2009) Distribution, elimination, and biopersistence to 90 days of a systemically introduced 30 nm ceria-engineered nanomaterial in rats. Toxicol Sci 127:256–268
Zhang K, Holloway T, Bahoura M, Pradhan AK, Prabakaran R, Pradhan J, Smith S, Hall JC, Ramesh GT, Sahu DR, Huang JL (2009) Europium doped Gd2O3 and FeCo nanoparticles for biomedical application. Proc of SPIE 7291:729104–729110
Acknowledgements
This work was supported in part by Chinese Natural Science Foundation Project (21271059, 81200078, 21301046, 51302062), Research Fund for the Doctoral Program of Higher Education of China (20111301110004, 20131301120004), the Outstanding Youth Fund Project (No. Y2012007), the China Postdoctoral Science Foundation (2013M530119), the Natural Science Foundation of Hebei Province (B2012201074), and Hundred Excellent Innovation Talents Supporting Project of Hebei Province (BR2-202), Training Program for Innovative Research Team and Leading Talent in Hebei Province University (LJRC024), and SRF for ROCS, SEM.
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Huifang Liu and Cuimiao Zhang have contributed equally to the study.
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Liu, H., Zhang, C., Tan, Y. et al. Biodistribution and toxicity assessment of europium-doped Gd2O3 nanotubes in mice after intraperitoneal injection. J Nanopart Res 16, 2303 (2014). https://doi.org/10.1007/s11051-014-2303-8
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DOI: https://doi.org/10.1007/s11051-014-2303-8