臺灣博碩士論文加值系統

奈米銀微粒具有特殊的物理化學特性，例如導電性好、穩定性佳且具有抗菌能力等特性，因此奈米銀微粒從先進的科技到醫學技術及民生用品皆被廣泛的應用，但同時也增加環境及人體暴露到奈米銀微粒的機會。儘管奈米銀微粒被大量地使用，但其對生物體的毒性效應資訊仍然相當缺乏，也因此奈米材料的物質安全資料表(SDSs)無法完整的被建立。斑馬魚具有飼養成本低、短時間內可大量繁殖、胚胎透明、胚胎發育時間快等優點，因此被認為是一個良好的動物模式，國際標準組織(International Organization for Standardization;ISO)也將斑馬魚列為奈米毒性測試的建議動物模式，而歐洲經濟合作暨發展組織 (Organisation for Economic Co-operation and Development; OECD)也已經建立數個使用斑馬魚作為毒性測試之指引。因此本研究利用斑馬魚模式探討以2-氨基乙硫醇修飾之大粒徑(Large size cysteamine-modified silver nanoparticle; LAS)與小粒徑(Small size cysteamine-modified silver nanoparticle; SAS)奈米銀微粒對斑馬魚不同胚胎發育階段之毒性效應，並且蒐集、整理及歸納現有的奈米銀微粒物質安全資料表，將可行的實驗數據應用於安全資料表的毒性資料或生態資料之項目。本研究先製備LAS (55.6±13.8 nm)及SAS (30.0±7.3 nm)，並測定其物化特性。將斑馬魚胚胎暴露於製備的奈米銀溶液中，於28℃培養至不同的發育時期，每日更換暴露溶液並觀察記錄存活率與畸形狀態，於試驗終點分析包含氧化壓力等毒性效應。本研究也使用Tg(LFABP:EGFP)肝臟基因轉殖斑馬魚、Tg(IFABP:dsRed)腸道基因轉殖斑馬魚以及huORFZ基因轉殖斑馬魚，分析奈米銀微粒造成的肝臟、腸道之發育影響及內質網壓力。此外，本研究也利用網路搜尋的方式，收集由供應商或製造商提供的19件奈米銀微粒物質安全資料表，並且進行內容的分析及整合。由時序性存活率(time-course survivorship)毒性試驗結果指出，斑馬魚胚胎分別暴露LAS及SAS後，其胚胎存活率皆隨著濃度增加而下降，存在劑量效應關係，並且LAS之毒性高於SAS。由胚胎存活率試驗結果也發現，斑馬魚胚胎發育的早期階段比後期階段對於奈米銀微粒具有較高的敏感性。奈米銀微粒亦會引起斑馬魚胚胎發育的異常，包括卵黃的不透明或水腫、心包膜水腫、體軸彎曲、以及胚胎發育延遲。利用螢光標記的奈米銀微粒測試後發現，LAS及SAS皆會穿過卵膜進入胚胎，而LAS進入胚胎之含量較SAS多。另外，奈米銀微粒會在胚胎的腸道及肝臟誘發氧化壓力，並造成肝細胞與腸道細胞受損。奈米銀微粒也會使胚胎產生內質網壓力，暴露LAS的胚胎其內質網壓力會表現在肝臟及腸道，而暴露SAS的胚胎則表現在卵黃囊的表面。而奈米銀微粒也會造成溶酶體的活性增加，可能也會誘發自體吞噬的作用。本研究也觀察到有凋亡細胞的產生，可能是造成胚胎畸形或發育遲緩的原因之一。在奈米物質安全資料表中，大多數奈米銀SDSs的內容並未包含充分的奈米材料安全資訊，例如奈米材料的毒性和物化特性，因此我們根據 ISO_TR_13014及13329（2012）之技術指南，將蒐集之文獻以及本研究分析結果，包含前述的存活率毒性試驗結果計算所得之該奈米物質的LD50及EC50，填入物化特性、毒理及生態毒性資訊的項目，提供初步的奈米銀SDSs模板及相關資訊。

Due to nanoparticles have unique physical and chemical properties, nanotechnology is rapidly growing with nanoparticles produced and utilized in a wide range of commercial products throughout the world. Silver nanoparticles (AgNPs) are the most commonly used among nanomaterials, which is a consequence of the above-noted antimicrobial properties of Ag. AgNPs are extensively used in electronics, catalysts, biosensors, medical devices, cosmetics and large commercial antibacterial products. These wide applications increase human and environment exposure and thus the potential risk related to their short- and long-term toxicity. The purpose of this study is to investigate the toxic effects and mechanism of AgNPs on zebrafish embryos. The results indicated zebrafish embryos exposed with AgNPs lead to reduce the survival ratios in a size-, dose-, and time dependent manner. The embryos treated with the AgNPs develop into abnormal phenotypes (abnormal jaw, axis flexure, pericardial edema, and yolk sac edema) and developmental retard. Our results implied that AgNPs-induced toxicity include oxidative stress, ER stress and apoptosis by particle can uptake into the embryos via chorion. These results show that different size of the AgNPs can trigger different toxicity, the large size cysteaamine-modified AgNPs were more toxic than small size cysteaamine-modified AgNPs. By comparing the safety material data sheets (SDSs) information between silver nano-sized and silver bulk-sized materials and performing current knowledge integration, we can provide more valid information on hazard identification and toxicological information of nano-safety data sheets.

第一章、序論 1
第二章、文獻回顧 2
第一節、奈米材料之應用 2
第二節、奈米材料物化特性及其潛在生物效應 2
第三節、奈米銀微粒之應用及表面修飾的效應 3
第四節、奈米銀微粒於in vitro與in vivo之毒性效應 4
第五節、奈米微粒生物危害評估動物(體內)模式 — 斑馬魚 6
第六節、奈米微粒之毒性機制與重要生物指標 13
第七節、奈米微粒物質安全資料表(MSDS)之發展需求與建立 17
第三章、研究目的 20
第四章、研究材料與方法 21
第一節、研究材料 21
第二節、研究方法與實驗步驟 25
一、奈米銀微粒合成 25
二、奈米銀微粒之物化特性分析方法 26
三、斑馬魚飼養 (Zebrafish husbandry) 27
四、斑馬魚配對方法 (Breeding of zebrafish embryos) 28
五、斑馬魚胚胎毒性試驗 28
六、斑馬魚胚胎毒性試驗生物指標 29
七、氧化壓力(Oxidative Stress)分析 29
八、以huORFZ基因轉殖斑馬魚分析奈米銀在斑馬魚誘發的內質網壓力 30
九、以Tg(LFABP:EGFP)肝臟基因轉殖斑馬魚及Tg(IFABP:dsRed)腸道基因轉殖斑馬魚評估奈米銀對標的器官的發育影響 30
十、細胞凋亡試驗-Whole-mount TUNEL assay 30
十一、斑馬魚胚胎之奈米銀微粒分布 30
十二、斑馬魚胚胎內之銀離子含量 31
十三、溶酶體活性(Lysosomal activity)分析 32
十四、免疫螢光染色(Whole-mount immunostaining) 32
十五、西方墨點法(Western Blot)分析 33
十六、統計分析 34
第五章、研究架構 35
第六章、研究結果 36
第一節、奈米銀微粒物化特性分析 36
第二節、2-氨基乙硫醇奈米銀微粒對於斑馬魚胚胎之毒性結果 36
第三節、斑馬魚胚胎暴露奈米銀微粒之外觀變化與畸形反應 37
第四節、暴露奈米銀微粒影響斑馬魚胚胎的發育 37
第五節、暴露奈米銀微粒後進行氧化壓力試驗 38
第六節、暴露奈米銀微粒後胚胎標的器官的影響 39
第七節、斑馬魚胚胎暴露奈米銀微粒之分布情形 39
第八節、斑馬魚胚胎暴露奈米銀微粒之銀離子含量測定 40
第九節、以huORFZ基因轉殖斑馬魚分析奈米銀在斑馬魚誘發的內質網壓力 40
第十節、暴露奈米銀微粒後以LysoTracker進行溶酶體活性的偵測 40
第十一節、暴露奈米銀微粒後細胞凋亡分析 40
第十二節、暴露奈米銀微粒後誘發細胞自體吞噬與內質網壓力之相關蛋白表現 41
第七章、討論 42
第八章、結論及建議 47
第九章、參考文獻 48
圖表 56

Ahamed M, Alsalhi MS, Siddiqui MK. 2010. Silver nanoparticle applications and human health. Clinica chimica acta; International Journal of Clinical Chemistry 411:1841-1848.
Ajayan PM. 1999. Nanotubes from carbon. Chemical reviews 99:1787-1800.
Arora S, Jain J, Rajwade JM, Paknikar KM. 2009. Interactions of silver nanoparticles with primary mouse fibroblasts and liver cells. Toxicology and Applied Pharmacology 236:310-318.
Asharani PV, Lian Wu Y, Gong Z, Valiyaveettil S. 2008. Toxicity of silver nanoparticles in zebrafish models. Nanotechnology 19:255102.
Baker RE, Schnell S. 2009. How can mathematics help us explore vertebrate segmentation? HFSP journal 3:1-5.
Berry JP, Gantar M, Gibbs PD, Schmale MC. 2007. The zebrafish (danio rerio) embryo as a model system for identification and characterization of developmental toxins from marine and freshwater microalgae. Comparative Biochemistry and Physiology Part C: Toxicology ＆ Pharmacology 145:61-72.
Blader P, Strähle U. 2000. Zebrafish developmental genetics and central nervous system development. Human Molecular Genetics 9:945-951.
Blaser SA, Scheringer M, Macleod M, Hungerbuhler K. 2008. Estimation of cumulative aquatic exposure and risk due to silver: Contribution of nano-functionalized plastics and textiles. The Science of the Total Environment 390:396-409.
Bohnsack JP, Assemi S, Miller JD, Furgeson DY. 2012. The primacy of physicochemical characterization of nanomaterials for reliable toxicity assessment: A review of the zebrafish nanotoxicology model. Nanotoxicity: Methods and Protocols:261-316.
Bonsignorio D, Perego L, Del Giacco L, Cotelli F. 1996. Structure and macromolecular composition of the zebrafish egg chorion. Zygote (Cambridge, England) 4:101-108.
Browning LM, Lee KJ, Nallathamby PD, Xu X-HN. 2013. Silver nanoparticles incite size-and dose-dependent developmental phenotypes and nanotoxicity in zebrafish embryos. Chemical Research in Toxicology 26:1503-1513.
Brustein E, Saint-Amant L, Buss RR, Chong M, McDearmid JR, Drapeau P. 2003. Steps during the development of the zebrafish locomotor network. Journal of Physiology-Paris 97:77-86.
Buttner JK, Soderberg R, Terlizzi D. 1993. An introduction to water chemistry in freshwater aquaculture. Nrac fact sheet no. 170.
Carlson C, Hussain SM, Schrand AM, Braydich-Stolle LK, Hess KL, Jones RL, et al. 2008. Unique cellular interaction of silver nanoparticles: Size-dependent generation of reactive oxygen species. The Journal of Physical Chemistry B 112:13608-13619.
Chargui A, Zekri S, Jacquillet G, Rubera I, Ilie M, Belaid A, et al. 2011. Cadmium-induced autophagy in rat kidney: An early biomarker of subtoxic exposure. Toxicological Sciences 121:31-42.
Chen EY, Wang YC, Chen CS, Chin WC. 2010. Functionalized positive nanoparticles reduce mucin swelling and dispersion. PloS One 5:15434.
Chen L, Miao Y, Chen L, Jin P, Zha Y, Chai Y, et al. 2013. The role of elevated autophagy on the synaptic plasticity impairment caused by cdse/zns quantum dots. Biomaterials 34:10172-10181.
Chen R, Huo L, Shi X, Bai R, Zhang Z, Zhao Y, et al. 2014. Endoplasmic reticulum stress induced by zinc oxide nanoparticles is an earlier biomarker for nanotoxicological evaluation. ACS Nano 8:2562-2574.
Cheng J, Flahaut E, Cheng SH. 2007. Effect of carbon nanotubes on developing zebrafish (danio rerio) embryos. Environmental Toxicology and Chemistry 26:708-716.
Choi JE, Kim S, Ahn JH, Youn P, Kang JS, Park K, et al. 2010. Induction of oxidative stress and apoptosis by silver nanoparticles in the liver of adult zebrafish. Aquatic Toxicology 100:151-159.
Christen V, Capelle M, Fent K. 2013. Silver nanoparticles induce endoplasmatic reticulum stress response in zebrafish. Toxicology and Applied Pharmacology 272:519-528.
Cui B, Ren L, Xu Q-H, Yin L-Y, Zhou X-Y, Liu J-X. 2016. Silver_ nanoparticles inhibited erythrogenesis during zebrafish embryogenesis. Aquatic Toxicology.
Cumano A, Godin I. 2007. Ontogeny of the hematopoietic system. Annu Rev Immunol 25:745-785.
Dai Y-J, Jia Y-F, Chen N, Bian W-P, Li Q-K, Ma Y-B, et al. 2014. Zebrafish as a model system to study toxicology. Environmental Toxicology and Chemistry 33:11-17.
Dawson M, Wirtz D, Hanes J. 2003. Enhanced viscoelasticity of human cystic fibrotic sputum correlates with increasing microheterogeneity in particle transport. The Journal of Biological Chemistry 278:50393-50401.
De Esch C, Slieker R, Wolterbeek A, Woutersen R, de Groot D. 2012. Zebrafish as potential model for developmental neurotoxicity testing: A mini review. Neurotoxicology and Teratology 34:545-553.
Fadool JM, Dowling JE. 2008. Zebrafish: A model system for the study of eye genetics. Progress in Retinal and Eye Research 27:89-110.
Fako VE, Furgeson DY. 2009. Zebrafish as a correlative and predictive model for assessing biomaterial nanotoxicity. Advanced Drug Delivery reviews 61:478-486.
Fent K, Weisbrod CJ, Wirth-Heller A, Pieles U. 2010. Assessment of uptake and toxicity of fluorescent silica nanoparticles in zebrafish (danio rerio) early life stages. Aquatic Toxicology 100:218-228.
Fluke C. 1993. Material safety data sheets. Journal of Healthcare Materiel Management 11:64-67.
Fubini B, Ghiazza M, Fenoglio I. 2010. Physico-chemical features of engineered nanoparticles relevant to their toxicity. Nanotoxicology 4:347-363.
Giudicelli F, Özbudak EM, Wright GJ, Lewis J. 2007. Setting the tempo in development: An investigation of the zebrafish somite clock mechanism. PLoS Biol 5:e150.
Glass AS, Dahm R. 2004. The zebrafish as a model organism for eye development. Ophthalmic research 36:4-24.
Goncalves SP, Strauss M, Delite FS, Clemente Z, Castro VL, Martinez DS. 2016. Activated carbon from pyrolysed sugarcane bagasse: Silver nanoparticle modification and ecotoxicity assessment. The Science of the Total Environment.
Guo L, Nie J, Du B, Peng Z, Tesche B, Kleinermanns K. 2008. Thermoresponsive polymer-stabilized silver nanoparticles. Journal of Colloid and Interface Science 319:175-181.
Haffter P, Granato M, Brand M, Mullins MC, Hammerschmidt M, Kane DA, et al. 1996. The identification of genes with unique and essential functions in the development of the zebrafish, danio rerio. Development (Cambridge, England) 123:1-36.
Halliwell B, Chirico S. 1993. Lipid peroxidation: Its mechanism, measurement, and significance. The American Journal of Clinical Nutrition 57:715S-724S.
Hill AJ, Bello SM, Prasch AL, Peterson RE, Heideman W. 2004. Water permeability and tcdd-induced edema in zebrafish early-life stages. Toxicological Sciences 78:78-87.
Huo L, Chen R, Zhao L, Shi X, Bai R, Long D, et al. 2015. Silver nanoparticles activate endoplasmic reticulum stress signaling pathway in cell and mouse models: The role in toxicity evaluation. Biomaterials 61:307-315.
Hwang P-P. 2009. Ion uptake and acid secretion in zebrafish (danio rerio). Journal of Experimental Biology 212:1745-1752.
Kahru A, Dubourguier HC. 2010. From ecotoxicology to nanoecotoxicology. Toxicology 269:105-119.
Kang R, Zeh H, Lotze M, Tang D. 2011. The beclin 1 network regulates autophagy and apoptosis. Cell Death ＆ Differentiation 18:571-580.
Karna P, Zughaier S, Pannu V, Simmons R, Narayan S, Aneja R. 2010. Induction of reactive oxygen species-mediated autophagy by a novel microtubule-modulating agent. Journal of Biological Chemistry 285:18737-18748.
Kikuta H, Laplante M, Navratilova P, Komisarczuk AZ, Engström PG, Fredman D, et al. 2007. Genomic regulatory blocks encompass multiple neighboring genes and maintain conserved synteny in vertebrates. Genome Research 17:545-555.
Kim HR, Shin DY, Park YJ, Park CW, Oh SM, Chung KH. 2014. Silver nanoparticles induce p53-mediated apoptosis in human bronchial epithelial (beas-2b) cells. The Journal of Toxicological Sciences 39:401-412.
Kim KT, Tanguay RL. 2014. The role of chorion on toxicity of silver nanoparticles in the embryonic zebrafish assay. Environmental Health and Toxicology 29:2014021.
Kim YS, Kim JS, Cho HS, Rha DS, Kim JM, Park JD, et al. 2008. Twenty-eight-day oral toxicity, genotoxicity, and gender-related tissue distribution of silver nanoparticles in sprague-dawley rats. Inhalation Toxicology 20:575-583.
Kimmel CB, Ballard WW, Kimmel SR, Ullmann B, Schilling TF. 1995. Stages of embryonic development of the zebrafish. Developmental Dynamics : an official publication of the American Association of Anatomists 203:253-310.
Kolp P, Sattler B, Blayney M, Sherwood T. 1993. Comprehensibility of material safety data sheets. American Journal of Industrial Medicine 23:135-141.
Kovvuru P, Mancilla PE, Shirode AB, Murray TM, Begley TJ, Reliene R. 2015. Oral ingestion of silver nanoparticles induces genomic instability and DNA damage in multiple tissues. Nanotoxicology 9:162-171.
Kroemer G, Mariño G, Levine B. 2010. Autophagy and the integrated stress response. Molecular Cell 40:280-293.
Lee JH, Kuk WK, Kwon M, Lee JH, Lee KS, Yu IJ. 2013. Evaluation of information in nanomaterial safety data sheets and development of international standard for guidance on preparation of nanomaterial safety data sheets. Nanotoxicology 7:338-345.
Lee KJ, Browning LM, Nallathamby PD, Desai T, Cherukuri PK, Xu X-HN. 2012. In vivo quantitative study of sized-dependent transport and toxicity of single silver nanoparticles using zebrafish embryos. Chemical Research in Toxicology 25:1029-1046.
Lee Y-H, Cheng F-Y, Chiu H-W, Tsai J-C, Fang C-Y, Chen C-W, et al. 2014. Cytotoxicity, oxidative stress, apoptosis and the autophagic effects of silver nanoparticles in mouse embryonic fibroblasts. Biomaterials 35:4706-4715.
Lewis KE, Eisen JS. 2003. From cells to circuits: Development of the zebrafish spinal cord. Progress in Neurobiology 69:419-449.
Lin S, Zhao Y, Nel AE, Lin S. 2013. Zebrafish: An in vivo model for nano ehs studies. Small (Weinheim an der Bergstrasse, Germany) 9:1608-1618.
Lister JA. 2002. Development of pigment cells in the zebrafish embryo. Microscopy Research and Technique 58:435-441.
Müller F, Blader P, Strähle U. 2002. Search for enhancers: Teleost models in comparative genomic and transgenic analysis of cis regulatory elements. Bioessays 24:564-572.
Malhotra JD, Kaufman RJ. 2007. Endoplasmic reticulum stress and oxidative stress: A vicious cycle or a double-edged sword? Antioxidants ＆ Redox Signaling 9:2277-2294.
Mao BH, Tsai JC, Chen CW, Yan SJ, Wang YJ. 2016. Mechanisms of silver nanoparticle-induced toxicity and important role of autophagy. Nanotoxicology:1-20.
Maynard AD, Kuempel ED. 2005. Airborne nanostructured particles and occupational health. J Nanopart Res 7:587-614.
McCollum CW, Ducharme NA, Bondesson M, Gustafsson JA. 2011. Developmental toxicity screening in zebrafish. Birth Defects Research Part C: Embryo Today: Reviews 93:67-114.
Morris A, Fadool J. 2005. Studying rod photoreceptor development in zebrafish. Physiology ＆ Behavior 86:306-313.
Nel A, Xia T, Mädler L, Li N. 2006. Toxic potential of materials at the nanolevel. Science 311:622-627.
Nornes S, Clarkson M, Mikkola I, Pedersen M, Bardsley A, Martinez JP, et al. 1998. Zebrafish contains two pax6 genes involved in eye development. Mechanisms of Development 77:185-196.
O'Neal DP, Hirsch LR, Halas NJ, Payne JD, West JL. 2004. Photo-thermal tumor ablation in mice using near infrared-absorbing nanoparticles. Cancer Letters 209:171-176.
Oberdorster G. 2010. Safety assessment for nanotechnology and nanomedicine: Concepts of nanotoxicology. Journal of Internal Medicine 267:89-105.
Ong KJ, Zhao X, Thistle ME, Maccormack TJ, Clark RJ, Ma G, et al. 2014. Mechanistic insights into the effect of nanoparticles on zebrafish hatch. Nanotoxicology 8:295-304.
Osborne OJ, Lin S, Chang CH, Ji Z, Yu X, Wang X, et al. 2015. Organ-specific and size-dependent ag nanoparticle toxicity in gills and intestines of adult zebrafish. ACS Nano 9:9573-9584.
Pluquet O, Pourtier A, Abbadie C. 2015. The unfolded protein response and cellular senescence. A review in the theme: Cellular mechanisms of endoplasmic reticulum stress signaling in health and disease. American Journal of Physiology Cell Physiology 308:C415-425.
Rao CN, Sood AK, Subrahmanyam KS, Govindaraj A. 2009. Graphene: The new two-dimensional nanomaterial. Angewandte Chemie 48:7752-7777.
Roy R, Singh SK, Chauhan L, Das M, Tripathi A, Dwivedi PD. 2014. Zinc oxide nanoparticles induce apoptosis by enhancement of autophagy via pi3k/akt/mtor inhibition. Toxicology Letters 227:29-40.
Scholz S, Fischer S, Gundel U, Kuster E, Luckenbach T, Voelker D. 2008. The zebrafish embryo model in environmental risk assessment--applications beyond acute toxicity testing. Environmental Science and Pollution Research International 15:394-404.
Scown TM, Santos EM, Johnston BD, Gaiser B, Baalousha M, Mitov S, et al. 2010. Effects of aqueous exposure to silver nanoparticles of different sizes in rainbow trout. Toxicological Sciences : an official journal of the Society of Toxicology 115:521-534.
Segner H. 2009. Zebrafish (danio rerio) as a model organism for investigating endocrine disruption. Comparative Biochemistry and Physiology Part C: Toxicology ＆ Pharmacology 149:187-195.
Seo H-C, Drivenes Ø, Ellingsen S, Fjose A. 1998. Expression of two zebrafish homologues of the murine six3 gene demarcates the initial eye primordia. Mechanisms of Development 73:45-57.
Shvedova AA, Pietroiusti A, Fadeel B, Kagan VE. 2012. Mechanisms of carbon nanotube-induced toxicity: Focus on oxidative stress. Toxicology and Applied Pharmacology 261:121-133.
Song B, Choi S, Han J. 2003. Developmental dynamics: An official publication of the american association of anatomists. Developmental Dynamics : an Official Publication of the American Association of Anatomists 227:91-103.
Stickney HL, Barresi MJ, Devoto SH. 2000. Somite development in zebrafish. Developmental Dynamics 219:287-303.
Tejamaya M, Romer I, Merrifield RC, Lead JR. 2012. Stability of citrate, pvp, and peg coated silver nanoparticles in ecotoxicology media. Environmental Science ＆ Technology 46:7011-7017.
Thisse C, Thisse B. 2008. High-resolution in situ hybridization to whole-mount zebrafish embryos. Nature Protocols 3:59-69.
Tiwari DK, Jin T, Behari J. 2011. Dose-dependent in-vivo toxicity assessment of silver nanoparticle in wistar rats. Toxicology Mechanisms and Methods 21:13-24.
Tiwari SB, Amiji MM. 2006. A review of nanocarrier-based cns delivery systems. Current Drug Delivery 3:219-232.
Tolaymat TM, El Badawy AM, Genaidy A, Scheckel KG, Luxton TP, Suidan M. 2010. An evidence-based environmental perspective of manufactured silver nanoparticle in syntheses and applications: A systematic review and critical appraisal of peer-reviewed scientific papers. Sci Total Environ 408:999-1006.
Verano-Braga T, Miethling-Graff R, Wojdyla K, Rogowska-Wrzesinska A, Brewer JR, Erdmann H, et al. 2014. Insights into the cellular response triggered by silver nanoparticles using quantitative proteomics. ACS Nano 8:2161-2175.
Wang JJ, Sanderson BJ, Wang H. 2007. Cyto- and genotoxicity of ultrafine tio2 particles in cultured human lymphoblastoid cells. Mutation Research 628:99-106.
Warheit DB, Borm PJ, Hennes C, Lademann J. 2007. Testing strategies to establish the safety of nanomaterials: Conclusions of an ecetoc workshop. Inhalation Toxicology 19:631-643.
Warner JH, Ito Y, Zaka M, Ge L, Akachi T, Okimoto H, et al. 2008. Rotating fullerene chains in carbon nanopeapods. Nano Letters 8:2328-2335.
Warren KS, Fishman MC. 1998. “Physiological genomics: Mutant screens in zebrafish. American Journal of Physiology-Heart and Circulatory Physiology 275:H1-H7.
Wei L, Lu J, Xu H, Patel A, Chen ZS, Chen G. 2015. Silver nanoparticles: Synthesis, properties, and therapeutic applications. Drug Discovery Today 20:595-601.
Wei Yh, Lu Cy, Lee Hc, Pang Cy, Ma Ys. 1998. Oxidative damage and mutation to mitochondrial DNA and age‐dependent decline of mitochondrial respiratory functiona. Annals of the New York Academy of Sciences 854:155-170.
Westerfield M. 1995. The zebrafish book: A guide for the laboratory use of zebrafish (brachydanio rerio):University of Oregon press.
Whitfield TT, Riley BB, Chiang MY, Phillips B. 2002. Development of the zebrafish inner ear. Developmental Dynamics 223:427-458.
Wu Y, Zhou Q. 2013. Silver nanoparticles cause oxidative damage and histological changes in medaka (oryzias latipes) after 14 days of exposure. Environmental Toxicology and Chemistry 32:165-173.
Xia G, Liu T, Wang Z, Hou Y, Dong L, Zhu J, et al. 2016. The effect of silver nanoparticles on zebrafish embryonic development and toxicology. Artificial cells, Nanomedicine, and Biotechnology 44:1116-1121.
Xin Q, Rotchell JM, Cheng J, Yi J, Zhang Q. 2015. Silver nanoparticles affect the neural development of zebrafish embryos. Journal of Applied Toxicology : JAT 35:1481-1492.
Xu L, Li X, Takemura T, Hanagata N, Wu G, Chou LL. 2012. Genotoxicity and molecular response of silver nanoparticle (np)-based hydrogel. Journal of Nanobiotechnology 10:16.
Zhang Q, Yang W, Man N, Zheng F, Shen Y, Sun K, et al. 2009. Autophagy-mediated chemosensitization in cancer cells by fullerene c60 nanocrystal. Autophagy 5:1107-1117.
Zhang R, Piao MJ, Kim KC, Kim AD, Choi J-Y, Choi J, et al. 2012. Endoplasmic reticulum stress signaling is involved in silver nanoparticles-induced apoptosis. The International Journal of Biochemistry ＆ Cell Biology 44:224-232.
Zhang T, Wang L, Chen Q, Chen C. 2014. Cytotoxic potential of silver nanoparticles. Yonsei Medical Journal 55:283-291.