基于亚细胞损伤的纳米材料毒性研究进展
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摘要
纳米材料具有独特的理化、光学、电学及抗菌特性,在生物医药领域具有潜在应用价值。随着纳米材料的广泛应用,其生物安全性引起了研究者们的关注。文章从纳米材料的特性出发,阐述了纳米材料在亚细胞水平上对细胞核、线粒体、内质网和溶酶体等细胞器的毒性作用研究进展,并对可能影响纳米材料亚细胞毒性的主要因素进行了归纳和讨论,对深入认识纳米材料毒效应和进一步开展纳米材料毒性研究提供参考。
Nanoparticles(NPs)have potential application in the field of biomedicine due to their unusual physicochemical,optical,and antibacterial properties. However,as particle size decreases,small size particles show increased toxicity. Meanwhile,their biosafety have attracted the attention of researchers. NPs interact with mammalian cells,and they can interfere with subcellular components,such as nuclei,mitochondria,endoplasmic reticulum and lysosomes,then causing apoptosis or necrosis. This brief review tries to summarize the toxicity effect of NPs on subcellular level,combining with the characteristics NPs.
Nanoparticles(NPs)have potential application in the field of biomedicine due to their unusual physicochemical,optical,and antibacterial properties. However,as particle size decreases,small size particles show increased toxicity. Meanwhile,their biosafety have attracted the attention of researchers. NPs interact with mammalian cells,and they can interfere with subcellular components,such as nuclei,mitochondria,endoplasmic reticulum and lysosomes,then causing apoptosis or necrosis. This brief review tries to summarize the toxicity effect of NPs on subcellular level,combining with the characteristics NPs.
引文
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[20]Peng F,Su YY,Zhong YL,et al. Subcellular distribution and cellular self-repair ability of fluorescent quantum dots emitting in the visible to near-infrared region[J]. Nano-technology,2017,28(4):045101
[21]Chu ZQ,Huang YJ,Tao Q,et al. Cellular uptake,evolu-tion,and excretion of silica nanoparticles in human cells[J]. Nanoscale,2011,3(8):3291-3299
[22] Lusk CP,Blobel G,King MC. Highway to the inner nuclear membrane:rules for the road[J]. Nature Rev Material,2007,8:414-420
[23]Zhu SJ,Zhou N,Hao ZY,et al. Photoluminescent gra-phene quantum dots for in vitro and in vivo bioimaging us-ing long wavelength emission[J]. RSC Adv,2015,5(49):39399-39403
[24]Soriano GB,Oliveira RD,Camilo FF,et al. Interaction of non-aqueous dispersions of Silver nanoparticles with cel-lular membrane models[J]. J Colloid Interface Sci,2017,496:111-117
[25]McShan D,Ray PC,Yu H. Molecular toxicity mechanism of nanosilver[J]. J Food Drug Anal,2014,22(1):116-127
[26] Zhang T,Wang YQ,Kong L,et al. Threshold dose of three types of quantum dots(QDs)induces oxidative stress trig-gers DNA damage and apoptosis in mouse fibroblast L929cells[J]. Int J Environ Res Public Health,2015,12(10):13435-13454
[27] Ahamed M,Karns M,Goodson M,et al. DNA damage re-sponse to different surface chemistry of Silver nanoparti-cles in mammalian cells[J]. Toxicol Appl Pharmacol,2008,233(3):404-410
[28]Pasquali F,Agrimonti C,Pagano L,et al. Nucleo-mito-chondrial interaction of yeast in response to cadmium sul-fide quantum dot exposure[J]. J Hazard Mater,2017,324(Pt B):744-752
[29]Nguyen KC,Rippstein P,Tayabali AF,et al. Mitochondrial toxicity of cadmium telluride quantum dot nanoparticles in mammalian hepatocytes[J]. Toxicol Sci,2015,146(1):31-42
[30]Maurer LL,Meyer JN. A systematic review of evidence for silver nanoparticle-induced mitochondrial toxicity[J]. En-viron Sci:Nano,2016,3(2):311-322
[31] Paesano L,Perotti A,Buschini A,et al. Markers for toxicity to HepG2exposed to Cadmium sulphide quantum dots;damage to mitochondria[J]. Toxicology,2016,374(1):18-28
[32] Song B,Zhou T,Yang WL,et al. Contribution of oxidative stress to TiO2nanoparticle-induced toxicity[J]. Environ Toxicol Pharmacol,2016,48:130-140
[33]Yu KN,Sung JH,Lee S,et al. Inhalation of titanium di-oxide induces endoplasmic reticulum stress-mediated au-tophagy and inflammation in mice[J]. Food Chem Toxi-col,2015,85:106-113
[34]Chen R,Huo LL,Shi XF,et al. Endoplasmic reticulum stress induced by Zinc oxide nanoparticles is an earlier biomarker for nanotoxicological evaluation[J]. ACS Nano,2014,8(3):2562-2574
[35]Yu KN,Chang SH,Park SJ,et al. Titanium dioxide nanoparticles induce endoplasmic reticulum stress-medi-ated autophagic cell death via mitochondria-associated en-doplasmic reticulum membrane disruption in normal lung cells[J]. PLoS One,2015,10(6):e0131208
[36]Simard JC,Vallieres F,De Liz RA,et al. Silver nanoparti-cles induce degradation of the endoplasmic reticulum stress sensor activating transcription factor-6 leading to activation of the NLRP-3 inflammasome[J]. J Biol Chem,2015,290(9):5926-5939
[37]Chen R,Zhao L,Bai R,et al. Silver nanoparticles induced oxidative and endoplasmic reticulum stresses in mouse tis-sues:implications for the development of acute toxicity af-ter intravenous administration[J]. Toxicol Res(Camb),2016,5(2):602-608
[38]Condello M,De Berardis B,Ammendolia MG,et al. ZnO nanoparticle tracking from uptake to genotoxic damage in humancoloncarcinomacells[J].ToxicolInVitro,2016,35:169-179
[39] Wang J,Yu YB,Lu K,et al. Silica nanoparticles induce autophagy dysfunction via lysosomal impairment and inhi-bition of autophagosome degradation in hepatocytes[J].Int J Nanomedicine,2017,12:809-825
[40] Pizzo E,Di Maro A. A new age for biomedical applica-tions of ribosome inactivating proteins(RIPs):from bio-conjugate to nanoconstructs[J]. J Biomed Sci,2016,23:54
[2]文若曦,江桂斌,周鑫.纳米银颗粒在大鼠中的生物富集行为研究[D].合肥:中国科学技术大学,2016
[3]邵二磊,吴明昊.防晒霜中纳米氧化锌和氧化钛在小鼠体内的代谢分布及口服毒性研究[D].上海:上海大学,2015
[4] Wen R,Yang X,Hu L,et al. Brain-targeted distribution and high retention of silver by chronic intranasal instilla-tion of silver nanoparticles and ions in sprague-dawley rats[J]. J Appl Toxicol,2016,36(3):445-453
[5]郝佳丽,刘庄.二维金属硫化物纳米材料在小鼠体内的分布,代谢及毒理学研究[D].苏州:苏州大学,2016
[6] Mrakovcic M,Absenger M,Riedl R,et al. Assessment of long-term effects of nanoparticles in a microcarrier cell culture system[J]. PLoS One,2013,8(2):e56791
[7] Zhang T,Hu YY,Tang M,et al. Liver toxicity of cadmium telluride quantum dots(CdTe QDs)due to oxidative stress in vitro and in vivo[J]. Int J Mol Sci,2015,16(10):23279-23299
[8]孙小怡,李艳博,郭彩霞.纳米材料诱导肺部疾病及其机制研究进展[J].天津医药,2016,44(11):1400-1404
[9]应佳丽,张婷,唐萌.金属氧化物纳米材料对L02细胞和Hep G2细胞毒性预测模型的构建[J].环境与职业医学,2016,33(3):209-214
[10] Kuang H,Yang P,Yang L,et al. Size dependent effect of ZnO nanoparticles on endoplasmic reticulum stress signal-ing pathway in murine liver[J]. J Hazard Mater,2016,317:119-126
[11]Kang H,Mintri S,Menon AV,et al. Pharmacokinetics,pharmacodynamics and toxicology of theranostic nanopar-ticles[J]. Nanoscale,2015,7(45):18848-18862
[12]赵光强,黄云超,李光剑,等.纳米二氧化硅在人支气管上皮细胞内的亚细胞分布和遗传毒性[J].中国肺癌杂志,2013,16(3):117-124
[13]夏阳,陈慧敏,胡姝颖,等.联合应用纳米金和磷酸钙骨水泥支架促进牙髓干细胞的增殖和成骨分化[J].南京医科大学学报(自然科学版),2018,38(5):590-594
[14]Cheng XL,ZhangWQ,Ji YL,etal. Revealing silvwe cyto-toxicity using Au nanorods/Ag shell nanostructures:dis-rupting cell membrane and causing apoptosis through oxi-dative damage[J]. RSC,2013,3:2296-2305
[15] Kumar S,Meena R,Paulraj R. Role of macrophage(M1and M2)in titanium-dioxide nanoparticle-induced oxida-tive stress and inflammatory response in rat[J]. Appl Bio-chem Biotechnol,2016,180(7):1257-1275
[16] Su Y,Hu M,Fan C,et al. The cytotoxicity of CdTe quan-tum dots and the relative contributions from released Cad-mium ions and nanoparticle properties[J]. Biomaterials,2010,31(18):4829-4834
[17] Dong P,Li JH,Xu SP,et al. Mitochondrial dysfunction in-duced by ultra-small silver nanoclusters with a distinct toxic mechanism[J]. J Hazard Mater,2016,308:139-148
[18] de Lima R,Seabra AB,Duran N. Silver nanoparticles:a brief review of cytotoxicity and genotoxicity of chemically and biogenically synthesized nanoparticles[J]. J Appl Toxicol,2012,32(11):867-879
[19] Park EJ,Choi DH,Kim Y,et al. Magnetic iron oxide nanoparticles induce autophagy preceding apoptosis through mitochondrial damage and ER stress in RAW264.7 cells[J]. Toxicol In Vitro,2014,28(8):1402-1412
[20]Peng F,Su YY,Zhong YL,et al. Subcellular distribution and cellular self-repair ability of fluorescent quantum dots emitting in the visible to near-infrared region[J]. Nano-technology,2017,28(4):045101
[21]Chu ZQ,Huang YJ,Tao Q,et al. Cellular uptake,evolu-tion,and excretion of silica nanoparticles in human cells[J]. Nanoscale,2011,3(8):3291-3299
[22] Lusk CP,Blobel G,King MC. Highway to the inner nuclear membrane:rules for the road[J]. Nature Rev Material,2007,8:414-420
[23]Zhu SJ,Zhou N,Hao ZY,et al. Photoluminescent gra-phene quantum dots for in vitro and in vivo bioimaging us-ing long wavelength emission[J]. RSC Adv,2015,5(49):39399-39403
[24]Soriano GB,Oliveira RD,Camilo FF,et al. Interaction of non-aqueous dispersions of Silver nanoparticles with cel-lular membrane models[J]. J Colloid Interface Sci,2017,496:111-117
[25]McShan D,Ray PC,Yu H. Molecular toxicity mechanism of nanosilver[J]. J Food Drug Anal,2014,22(1):116-127
[26] Zhang T,Wang YQ,Kong L,et al. Threshold dose of three types of quantum dots(QDs)induces oxidative stress trig-gers DNA damage and apoptosis in mouse fibroblast L929cells[J]. Int J Environ Res Public Health,2015,12(10):13435-13454
[27] Ahamed M,Karns M,Goodson M,et al. DNA damage re-sponse to different surface chemistry of Silver nanoparti-cles in mammalian cells[J]. Toxicol Appl Pharmacol,2008,233(3):404-410
[28]Pasquali F,Agrimonti C,Pagano L,et al. Nucleo-mito-chondrial interaction of yeast in response to cadmium sul-fide quantum dot exposure[J]. J Hazard Mater,2017,324(Pt B):744-752
[29]Nguyen KC,Rippstein P,Tayabali AF,et al. Mitochondrial toxicity of cadmium telluride quantum dot nanoparticles in mammalian hepatocytes[J]. Toxicol Sci,2015,146(1):31-42
[30]Maurer LL,Meyer JN. A systematic review of evidence for silver nanoparticle-induced mitochondrial toxicity[J]. En-viron Sci:Nano,2016,3(2):311-322
[31] Paesano L,Perotti A,Buschini A,et al. Markers for toxicity to HepG2exposed to Cadmium sulphide quantum dots;damage to mitochondria[J]. Toxicology,2016,374(1):18-28
[32] Song B,Zhou T,Yang WL,et al. Contribution of oxidative stress to TiO2nanoparticle-induced toxicity[J]. Environ Toxicol Pharmacol,2016,48:130-140
[33]Yu KN,Sung JH,Lee S,et al. Inhalation of titanium di-oxide induces endoplasmic reticulum stress-mediated au-tophagy and inflammation in mice[J]. Food Chem Toxi-col,2015,85:106-113
[34]Chen R,Huo LL,Shi XF,et al. Endoplasmic reticulum stress induced by Zinc oxide nanoparticles is an earlier biomarker for nanotoxicological evaluation[J]. ACS Nano,2014,8(3):2562-2574
[35]Yu KN,Chang SH,Park SJ,et al. Titanium dioxide nanoparticles induce endoplasmic reticulum stress-medi-ated autophagic cell death via mitochondria-associated en-doplasmic reticulum membrane disruption in normal lung cells[J]. PLoS One,2015,10(6):e0131208
[36]Simard JC,Vallieres F,De Liz RA,et al. Silver nanoparti-cles induce degradation of the endoplasmic reticulum stress sensor activating transcription factor-6 leading to activation of the NLRP-3 inflammasome[J]. J Biol Chem,2015,290(9):5926-5939
[37]Chen R,Zhao L,Bai R,et al. Silver nanoparticles induced oxidative and endoplasmic reticulum stresses in mouse tis-sues:implications for the development of acute toxicity af-ter intravenous administration[J]. Toxicol Res(Camb),2016,5(2):602-608
[38]Condello M,De Berardis B,Ammendolia MG,et al. ZnO nanoparticle tracking from uptake to genotoxic damage in humancoloncarcinomacells[J].ToxicolInVitro,2016,35:169-179
[39] Wang J,Yu YB,Lu K,et al. Silica nanoparticles induce autophagy dysfunction via lysosomal impairment and inhi-bition of autophagosome degradation in hepatocytes[J].Int J Nanomedicine,2017,12:809-825
[40] Pizzo E,Di Maro A. A new age for biomedical applica-tions of ribosome inactivating proteins(RIPs):from bio-conjugate to nanoconstructs[J]. J Biomed Sci,2016,23:54
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