Abstract
Different types of nanomaterials possess excellent physical and chemical properties. Nanoparticles (NPs) have been implicated for use in drug and gene delivery. Several in vitro and in vivo studies suggest the cytotoxic and proinflammatory potential of NPs. Further, parenteral administration of NPs results in their accumulation in several tissues. The possible mechanism of toxicity appears to be production of free radicals, mitogen activated protein kinase (MAPK) activation and translocation of transcription factors from cytoplasm to nucleus. This leads to induction of apoptosis, growth arrest, and cell death. Further, factors like nuclear factor-κB (NF-κB) lead to production of proinflammatory cytokines. The present review focuses on the cytotoxicity, biodistribution, and mechanism of NPs toxicity with special emphasis on carbon nanotubes (CNTs) toxicity.
Keywords
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Abbreviations
- ADME:
-
Absorption, distribution, metabolism, and excretion
- Akt:
-
Protein kinase B
- AP-1:
-
Activator protein 1
- BAL:
-
Bronchoalveolar lavage
- BaP:
-
Benzo[a]pyrene
- BBB:
-
Blood brain barrier
- CNTs:
-
Carbon nanotubes
- F-CNTs:
-
Functionalized CNTs
- GRAS:
-
Generally regarded as safe
- IL:
-
Interleukins
- LDL:
-
Low density lipoproteins
- MAPK:
-
Mitogen activated protein kinase
- MCP 1:
-
Monocyte chemoattractant protein-1
- MMP:
-
Mitochondrial membrane potential
- MN:
-
Micronucleus
- mt DNA:
-
Mitochondrial DNA
- MWCNTs:
-
Multi walled carbon nanotubes
- NF-κB:
-
Nuclear factor-κB
- NIR:
-
Near infrared
- NPs:
-
Nanoparticles
- PARP:
-
Poly ADP ribose polymerase
- PDGF:
-
Platelet derived growth factor
- PLGA:
-
Poly(lactic-co-glycolic acid)
- QDs:
-
Quantum dots
- RES:
-
Reticuloendothelial system
- ROS:
-
Reactive oxygen species
- SEM:
-
Scanning electron microscope
- SWCNTs:
-
Single walled carbon nanotubes
- TEM:
-
Transmission electron microscope
- TNF-α:
-
Tumor necrosis factor alpha
- α-SMA:
-
Alpha smooth muscle actin
References
Martin RS, Mather TA, Pyle DM, Power M, Allen AG, Aiuppa A, Horwell CJ, Ward EPW (2008) Composition-resolved size distributions of volcanic aerosols in the Mt. Etna plumes. J Geophys Res 113, D17211:1–17
Murr LE, Soto KF, Garza KM, Guerrero PA, Martinez F, Esquivel EV, Ramirez DA, Shi Y, Bang JJ, Venzor J 3rd (2006) Combustion-generated nanoparticulates in the El Paso, TX, USA / Juarez, Mexico Metroplex: their comparative characterization and potential for adverse health effects. Int J Environ Res Public Health 3:48–66
Murr LE (2007) Nanoparticulate materials in antiquity: the good, the bad and the ugly. Microsc Microanal 13:1118–1119
Farokhzad OC, Langer R (2009) Impact of nanotechnology on drug delivery. ACS Nano 3:16–20
Hong H, Gao T, Cai W (2009) Molecular imaging with single-walled carbon nanotubes. Nano Today 4:252–261
Sandhiya S, Dkhar SA, Surendiran A (2009) Emerging trends of nanomedicine: an overview. Fundam Clin Pharmacol 23:263–269
Moghimi SM, Hunter AC, Murray JC (2005) Nanomedicine: current status and future prospects. FASEB J 19:311–330
Yu X, Zhang Y, Chen C, Yao Q, Li M (2010) Targeted drug delivery in pancreatic cancer. Biochim Biophys Acta 1805:97–104
Tang MF, Lei L, Guo SR, Huang WL (2010) Recent progress in nanotechnology for cancer therapy. Chin J Cancer 29:775–780
Rao J (2008) Shedding light on tumors using nanoparticles. ACS Nano 2:1984–1986
Inoue K-i, Takano H, Yanagisawa R, Koike E, Shimada A (2009) Size effects of latex nanomaterials on lung inflammation in mice. Toxicol Appl Pharmacol 234:68–76
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
Monteiro-Riviere NA, Inman AO, Zhang LW (2009) Limitations and relative utility of screening assays to assess engineered nanoparticle toxicity in a human cell line. Toxicol Appl Pharmacol 234:222–235
Choi JY, Ramachandran G, Kandlikar M (2009) The impact of toxicity testing costs on nanomaterial regulation. Environ Sci Technol 43:3030–3034
Lee HM, Shin DM, Song HM, Yuk JM, Lee ZW, Lee SH, Hwang SM, Kim JM, Lee CS, Jo EK (2009) Nanoparticles up-regulate tumor necrosis factor-alpha and CXCL8 via reactive oxygen species and mitogen-activated protein kinase activation. Toxicol Appl Pharmacol 238:160–169
Radomski A, Jurasz P, Alonso-Escolano D, Drews M, Morandi M, Malinski T, Radomski MW (2005) Nanoparticle-induced platelet aggregation and vascular thrombosis. Br J Pharmacol 146:882–893
Singh N, Manshian B, Jenkins GJ, Griffiths SM, Williams PM, Maffeis TG, Wright CJ, Doak SH (2009) NanoGenotoxicology: the DNA damaging potential of engineered nanomaterials. Biomaterials 30:3891–3914
Murray AR, Kisin E, Leonard SS, Young SH, Kommineni C, Kagan VE, Castranova V, Shvedova AA (2009) Oxidative stress and inflammatory response in dermal toxicity of single-walled carbon nanotubes. Toxicology 257:161–171
Colvin VL (2003) The potential environmental impact of engineered nanomaterials. Nat Biotechnol 21:1166–1170
Shvedova AA, Kagan VE, Fadeel B (2010) Close encounters of the small kind: adverse effects of man-made materials interfacing with the nano-cosmos of biological systems. Annu Rev Pharmacol Toxicol 50:63–88
Stevens MM (2009) Toxicology: testing in the third dimension. Nat Nanotechnol 4:342–343
Prato M, Kostarelos K, Bianco A (2008) Functionalized carbon nanotubes in drug design and discovery. Acc Chem Res 41:60–68
Kam NW, O’Connell M, Wisdom JA, Dai H (2005) Carbon nanotubes as multifunctional biological transporters and near-infrared agents for selective cancer cell destruction. Proc Natl Acad Sci U S A 102:11600–11605
Kostarelos K, Bianco A, Prato M (2009) Promises, facts and challenges for carbon nanotubes in imaging and therapeutics. Nat Nanotechnol 4:627–633
Liu Z, Chen K, Davis C, Sherlock S, Cao Q, Chen X, Dai H (2008) Drug delivery with carbon nanotubes for in vivo cancer treatment. Cancer Res 68:6652–6660
Zhang Y, Bai Y, Yan B (2010) Functionalized carbon nanotubes for potential medicinal applications. Drug Discov Today 15:428–435
Bianco A (2004) Carbon nanotubes for the delivery of therapeutic molecules. Expert Opin Drug Deliv 1:57–65
Lacerda L, Bianco A, Prato M, Kostarelos K (2006) Carbon nanotubes as nanomedicines: from toxicology to pharmacology. Adv Drug Deliv Rev 58:1460–1470
Pantarotto D, Singh R, McCarthy D, Erhardt M, Briand JP, Prato M, Kostarelos K, Bianco A (2004) Functionalized carbon nanotubes for plasmid DNA gene delivery. Angew Chem Int Ed Engl 43:5242–5246
Pastorin G (2009) Crucial functionalizations of carbon nanotubes for improved drug delivery: a valuable option? Pharm Res 26:746–769
Fonseca C, Simoes S, Gaspar R (2002) Paclitaxel-loaded PLGA nanoparticles: preparation, physicochemical characterization and in vitro anti-tumoral activity. J Control Release 83:273–286
Lo CT, Van Tassel PR, Saltzman WM (2010) Poly(lactide-co-glycolide) nanoparticle assembly for highly efficient delivery of potent therapeutic agents from medical devices. Biomaterials 31:3631–3642
Wang ZH, Wang ZY, Sun CS, Wang CY, Jiang TY, Wang SL (2010) Trimethylated chitosan-conjugated PLGA nanoparticles for the delivery of drugs to the brain. Biomaterials 31:908–915
Choi HS, Liu W, Misra P, Tanaka E, Zimmer JP, Itty Ipe B, Bawendi MG, Frangioni JV (2007) Renal clearance of quantum dots. Nat Biotechnol 25:1165–1170
Michalet X, Pinaud FF, Bentolila LA, Tsay JM, Doose S, Li JJ, Sundaresan G, Wu AM, Gambhir SS, Weiss S (2005) Quantum dots for live cells, in vivo imaging, and diagnostics. Science 307:538–544
Erdely A, Hulderman T, Salmen R, Liston A, Zeidler-Erdely PC, Schwegler-Berry D, Castranova V, Koyama S, Kim YA, Endo M, Simeonova PP (2009) Cross-talk between lung and systemic circulation during carbon nanotube respiratory exposure. Potential biomarkers. Nano Lett 9:36–43
Ji Z, Zhang D, Li L, Shen X, Deng X, Dong L, Wu M, Liu Y (2009) The hepatotoxicity of multi-walled carbon nanotubes in mice. Nanotechnology 20:445101
Lacerda L, Ali-Boucetta H, Herrero MA, Pastorin G, Bianco A, Prato M, Kostarelos K (2008) Tissue histology and physiology following intravenous administration of different types of functionalized multiwalled carbon nanotubes. Nanomedicine (Lond) 3:149–161
Muller J, Delos M, Panin N, Rabolli V, Huaux F, Lison D (2009) Absence of carcinogenic response to multiwall carbon nanotubes in a 2-year bioassay in the peritoneal cavity of the rat. Toxicol Sci 110:442–448
Schipper ML, Nakayama-Ratchford N, Davis CR, Kam NW, Chu P, Liu Z, Sun X, Dai H, Gambhir SS (2008) A pilot toxicology study of single-walled carbon nanotubes in a small sample of mice. Nat Nanotechnol 3:216–221
Singh R, Pantarotto D, Lacerda L, Pastorin G, Klumpp C, Prato M, Bianco A, Kostarelos K (2006) Tissue biodistribution and blood clearance rates of intravenously administered carbon nanotube radiotracers. Proc Natl Acad Sci U S A 103:3357–3362
Chan VS (2006) Nanomedicine: an unresolved regulatory issue. Regul Toxicol Pharmacol 46:218–224
Kipen HM, Laskin DL (2005) Smaller is not always better: nanotechnology yields nanotoxicology. Am J Physiol Lung Cell Mol Physiol 289:L696–L697
Oberdorster G, Oberdorster E, Oberdorster J (2005) Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 113:823–839
Selvi BR, Jagadeesan D, Suma BS, Nagashankar G, Arif M, Balasubramanyam K, Eswaramoorthy M, Kundu TK (2008) Intrinsically fluorescent carbon nanospheres as a nuclear targeting vector: delivery of membrane-impermeable molecule to modulate gene expression in vivo. Nano Lett 8:3182–3188
Levi-Polyachenko NH, Merkel EJ, Jones BT, Carroll DL, Stewart JH (2009) Rapid photothermal intracellular drug delivery using multiwalled carbon nanotubes. Mol Pharm 6:1092–1099
Ma L, Liu J, Li N, Wang J, Duan Y, Yan J, Liu H, Wang H, Hong F (2010) Oxidative stress in the brain of mice caused by translocated nanoparticulate TiO2 delivered to the abdominal cavity. Biomaterials 31:99–105
Belyanskaya L, Weigel S, Hirsch C, Tobler U, Krug HF, Wick P (2009) Effects of carbon nanotubes on primary neurons and glial cells. Neurotoxicology 30:702–711
Hu YL, Gao JQ (2010) Potential neurotoxicity of nanoparticles. Int J Pharm 394:115–121
Jones R (2009) It's not just about nanotoxicology. Nat Nanotechnol 4:615
Kim S, Choi JE, Choi J, Chung KH, Park K, Yi J, Ryu DY (2009) Oxidative stress-dependent toxicity of silver nanoparticles in human hepatoma cells. Toxicol In Vitro 23:1076–1084
Mayer A, Vadon M, Rinner B, Novak A, Wintersteiger R, Frohlich E (2009) The role of nanoparticle size in hemocompatibility. Toxicology 258:139–147
Napierska D, Thomassen LC, Rabolli V, Lison D, Gonzalez L, Kirsch-Volders M, Martens JA, Hoet PH (2009) Size-dependent cytotoxicity of monodisperse silica nanoparticles in human endothelial cells. Small 5:846–853
Valant J, Drobne D, Sepcic K, Jemec A, Kogej K, Kostanjsek R (2009) Hazardous potential of manufactured nanoparticles identified by in vivo assay. J Hazard Mater 171:160–165
Fischer HC, Chan WC (2007) Nanotoxicity: the growing need for in vivo study. Curr Opin Biotechnol 18:565–571
Fadeel B, Valerian H, Krug H, Shvedova A, Svartengren M, Tran L, Wiklund L (2007) There’s plenty of room at the forum: potential risks and safety assessment of engineered nanomaterials. Nanotoxicology 1:73–84
Ray PC, Yu H, Fu PP (2009) Toxicity and environmental risks of nanomaterials: challenges and future needs. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 27:1–35
Donaldson K, Stone V, Tran CL, Kreyling W, Borm PJ (2004) Nanotoxicology. Occup Environ Med 61:727–728
Haynes CL (2010) The emerging field of nanotoxicology. Anal Bioanal Chem 398:587–588
Service RF (2008) Science policy. Report faults U.S. strategy for nanotoxicology research. Science 322:1779
Kagan VE, Bayir H, Shvedova AA (2005) Nanomedicine and nanotoxicology: two sides of the same coin. Nanomedicine 1:313–316
Rzigalinski BA, Strobl JS (2009) Cadmium-containing nanoparticles: perspectives on pharmacology and toxicology of quantum dots. Toxicol Appl Pharmacol 238:280–288
Kunzmann A, Andersson B, Thurnherr T, Krug H, Scheynius A, Fadeel B (2011) Toxicology of engineered nanomaterials: focus on biocompatibility, biodistribution and biodegradation. Biochim Biophys Acta 1810(3):361–373
Suh WH, Suslick KS, Stucky GD, Suh YH (2009) Nanotechnology, nanotoxicology, and neuroscience. Prog Neurobiol 87:133–170
Kroll A, Pillukat MH, Hahn D, Schnekenburger J (2009) Current in vitro methods in nanoparticle risk assessment: limitations and challenges. Eur J Pharm Biopharm 72:370–377
Kahru A, Savolainen K (2010) Potential hazard of nanoparticles: from properties to biological and environmental effects. Toxicology 269:89–91
Casalsa E, Vázquez-Camposa S, Bastús NG, Puntes V (2008) Distribution and potential toxicity of engineered inorganic nanoparticles and carbon nanostructures in biological systems. Trends Anal Chem 27:672–683
Jones CF, Grainger DW (2009) In vitro assessments of nanomaterial toxicity. Adv Drug Deliv Rev 61:438–456
Geys J, Nemery B, Hoet PH (2010) Assay conditions can influence the outcome of cytotoxicity tests of nanomaterials: better assay characterization is needed to compare studies. Toxicol In Vitro 24:620–629
Clift MJ, Gehr P, Rothen-Rutishauser B (2011) Nanotoxicology: a perspective and discussion of whether or not in vitro testing is a valid alternative. Arch Toxicol 85:723–731
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
Nishimori H, Kondoh M, Isoda K, Tsunoda S, Tsutsumi Y, Yagi K (2009) Silica nanoparticles as hepatotoxicants. Eur J Pharm Biopharm 72:496–501
Aggarwal P, Hall JB, McLeland CB, Dobrovolskaia MA, McNeil SE (2009) Nanoparticle interaction with plasma proteins as it relates to particle biodistribution, biocompatibility and therapeutic efficacy. Adv Drug Deliv Rev 61:428–437
Li SD, Huang L (2008) Pharmacokinetics and biodistribution of nanoparticles. Mol Pharm 5:496–504
Muller J, Huaux F, Lison D (2006) Respiratory toxicity of carbon nanotubes: how worried should we be? Carbon 44:1048–1056
Lam CW, James JT, McCluskey R, Hunter RL (2004) Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation. Toxicol Sci 77:126–134
Chou CC, Hsiao HY, Hong QS, Chen CH, Peng YW, Chen HW, Yang PC (2008) Single-walled carbon nanotubes can induce pulmonary injury in mouse model. Nano Lett 8:437–445
Liu Z, Davis C, Cai W, He L, Chen X, Dai H (2008) Circulation and long-term fate of functionalized, biocompatible single-walled carbon nanotubes in mice probed by Raman spectroscopy. Proc Natl Acad Sci U S A 105:1410–1415
Fadeel B, Garcia-Bennett AE (2010) Better safe than sorry: understanding the toxicological properties of inorganic nanoparticles manufactured for biomedical applications. Adv Drug Deliv Rev 62:362–374
Mutlu GM, Budinger GR, Green AA, Urich D, Soberanes S, Chiarella SE, Alheid GF, McCrimmon DR, Szleifer I, Hersam MC (2010) Biocompatible nanoscale dispersion of single-walled carbon nanotubes minimizes in vivo pulmonary toxicity. Nano Lett 10:1664–1670
Vittorio O, Raffa V, Cuschieri A (2009) Influence of purity and surface oxidation on cytotoxicity of multiwalled carbon nanotubes with human neuroblastoma cells. Nanomedicine 5:424–431
Ryman-Rasmussen JP, Riviere JE, Monteiro-Riviere NA (2007) Surface coatings determine cytotoxicity and irritation potential of quantum dot nanoparticles in epidermal keratinocytes. J Invest Dermatol 127:143–153
Grabinski C, Hussain S, Lafdi K, Braydich-Stolle L, Schlager J (2007) Effect of particle dimension on biocompatibility of carbon nanomaterials. Carbon 45:2828–2835
Reddy AR, Reddy YN, Krishna DR, Himabindu V (2010) Multi wall carbon nanotubes induce oxidative stress and cytotoxicity in human embryonic kidney (HEK293) cells. Toxicology 272:11–16
Carlson C, Hussain SM, Schrand AM, Braydich-Stolle LK, Hess KL, Jones RL, Schlager JJ (2008) Unique cellular interaction of silver nanoparticles: size-dependent generation of reactive oxygen species. J Phys Chem B 112:13608–13619
Fubini B, Ghiazza M, Fenoglio I (2010) Physico-chemical features of engineered nanoparticles relevant to their toxicity. Nanotoxicology 4:347–363
Ahamed M, Posgai R, Gorey TJ, Nielsen M, Hussain SM, Rowe JJ (2010) Silver nanoparticles induced heat shock protein 70, oxidative stress and apoptosis in Drosophila melanogaster. Toxicol Appl Pharmacol 242:263–269
Elgrabli D, Abella-Gallart S, Robidel F, Rogerieux F, Boczkowski J, Lacroix G (2008) Induction of apoptosis and absence of inflammation in rat lung after intratracheal instillation of multiwalled carbon nanotubes. Toxicology 253:131–136
Kang SJ, Kim BM, Lee YJ, Chung HW (2008) Titanium dioxide nanoparticles trigger p53-mediated damage response in peripheral blood lymphocytes. Environ Mol Mutagen 49:399–405
Moller P, Jacobsen NR, Folkmann JK, Danielsen PH, Mikkelsen L, Hemmingsen JG, Vesterdal LK, Forchhammer L, Wallin H, Loft S (2010) Role of oxidative damage in toxicity of particulates. Free Radic Res 44:1–46
Poma A, Di Giorgio ML (2008) Toxicogenomics to improve comprehension of the mechanisms underlying responses of in vitro and in vivo systems to nanomaterials: a review. Curr Genomics 9:571–585
Ye SF, Wu YH, Hou ZQ, Zhang QQ (2009) ROS and NF-kappaB are involved in upregulation of IL-8 in A549 cells exposed to multi-walled carbon nanotubes. Biochem Biophys Res Commun 379:643–648
Park EJ, Kim H, Kim Y, Yi J, Choi K, Park K (2010) Carbon fullerenes (C60s) can induce inflammatory responses in the lung of mice. Toxicol Appl Pharmacol 244:226–233
Park YH, Kim JN, Jeong SH, Choi JE, Lee SH, Choi BH, Lee JP, Sohn KH, Park KL, Kim MK, Son SW (2010) Assessment of dermal toxicity of nanosilica using cultured keratinocytes, a human skin equivalent model and an in vivo model. Toxicology 267:178–181
De Jong WH, Hagens WI, Krystek P, Burger MC, Sips AJ, Geertsma RE (2008) Particle size-dependent organ distribution of gold nanoparticles after intravenous administration. Biomaterials 29:1912–1919
Balasubramanian SK, Jittiwat J, Manikandan J, Ong CN, Yu LE, Ong WY (2010) Biodistribution of gold nanoparticles and gene expression changes in the liver and spleen after intravenous administration in rats. Biomaterials 31:2034–2042
Cho WS, Cho M, Jeong J, Choi M, Han BS, Shin HS, Hong J, Chung BH, Jeong J, Cho MH (2010) Size-dependent tissue kinetics of PEG-coated gold nanoparticles. Toxicol Appl Pharmacol 245:116–123
Li JJ, Hartono D, Ong CN, Bay BH, Yung LY (2010) Autophagy and oxidative stress associated with gold nanoparticles. Biomaterials 31:5996–6003
Ahamed M, Karns M, Goodson M, Rowe J, Hussain SM, Schlager JJ, Hong Y (2008) DNA damage response to different surface chemistry of silver nanoparticles in mammalian cells. Toxicol Appl Pharmacol 233:404–410
Chu M, Wu Q, Yang H, Yuan R, Hou S, Yang Y, Zou Y, Xu S, Xu K, Ji A, Sheng L (2010) Transfer of quantum dots from pregnant mice to pups across the placental barrier. Small 6:670–678
Rosas-Hernandez H, Jimenez-Badillo S, Martinez-Cuevas PP, Gracia-Espino E, Terrones H, Terrones M, Hussain SM, Ali SF, Gonzalez C (2009) Effects of 45-nm silver nanoparticles on coronary endothelial cells and isolated rat aortic rings. Toxicol Lett 191:305–313
Mo Y, Wan R, Chien S, Tollerud DJ, Zhang Q (2009) Activation of endothelial cells after exposure to ambient ultrafine particles: the role of NADPH oxidase. Toxicol Appl Pharmacol 236:183–193
Ema M, Kobayashi N, Naya M, Hanai S, Nakanishi J (2010) Reproductive and developmental toxicity studies of manufactured nanomaterials. Reprod Toxicol 30:343–352
Gao J, Wang HL, Shreve A, Iyer R (2010) Fullerene derivatives induce premature senescence: a new toxicity paradigm or novel biomedical applications. Toxicol Appl Pharmacol 244:130–143
Johnston HJ, Hutchison GR, Christensen FM, Aschberger K, Stone V (2010) The biological mechanisms and physicochemical characteristics responsible for driving fullerene toxicity. Toxicol Sci 114:162–182
Naha PC, Bhattacharya K, Tenuta T, Dawson KA, Lynch I, Gracia A, Lyng FM, Byrne HJ (2010) Intracellular localisation, geno- and cytotoxic response of polyN-isopropylacrylamide (PNIPAM) nanoparticles to human keratinocyte (HaCaT) and colon cells (SW 480). Toxicol Lett 198:134–143
Marquis BJ, Love SA, Braun KL, Haynes CL (2009) Analytical methods to assess nanoparticle toxicity. Analyst 134:425–439
Vega-Villa KR, Takemoto JK, Yanez JA, Remsberg CM, Forrest ML, Davies NM (2008) Clinical toxicities of nanocarrier systems. Adv Drug Deliv Rev 60:929–938
Lei R, Wu C, Yang B, Ma H, Shi C, Wang Q, Wang Q, Yuan Y, Liao M (2008) Integrated metabolomic analysis of the nano-sized copper particle-induced hepatotoxicity and nephrotoxicity in rats: a rapid in vivo screening method for nanotoxicity. Toxicol Appl Pharmacol 232:292–301
Bu Q, Yan G, Deng P, Peng F, Lin H, Xu Y, Cao Z, Zhou T, Xue A, Wang Y, Cen X, Zhao YL (2010) NMR-based metabonomic study of the sub-acute toxicity of titanium dioxide nanoparticles in rats after oral administration. Nanotechnology 21:125105
Lubick N (2008) Risks of nanotechnology remain uncertain. Environ Sci Technol 42:1821–1824
Seaton A, Tran L, Aitken R, Donaldson K (2010) Nanoparticles, human health hazard and regulation. J R Soc Interface 7(Suppl 1):S119–S129
Stone V, Donaldson K (2006) Nanotoxicology: signs of stress. Nat Nanotechnol 1:23–24
George S, Pokhrel S, Xia T, Gilbert B, Ji Z, Schowalter M, Rosenauer A, Damoiseaux R, Bradley KA, Madler L, Nel AE (2010) Use of a rapid cytotoxicity screening approach to engineer a safer zinc oxide nanoparticle through iron doping. ACS Nano 4:15–29
Meng H, Xia T, George S, Nel AE (2009) A predictive toxicological paradigm for the safety assessment of nanomaterials. ACS Nano 3:1620–1627
Foldvari M, Bagonluri M (2008) Carbon nanotubes as functional excipients for nanomedicines: II. Drug delivery and biocompatibility issues. Nanomedicine 4:183–200
Chikkaveeraiah BV, Bhirde A, Malhotra R, Patel V, Gutkind JS, Rusling JF (2009) Single-wall carbon nanotube forest arrays for immunoelectrochemical measurement of four protein biomarkers for prostate cancer. Anal Chem 81:9129–9134
Liu Z, Tabakman SM, Chen Z, Dai H (2009) Preparation of carbon nanotube bioconjugates for biomedical applications. Nat Protoc 4:1372–1382
Bianco A, Kostarelos K, Partidos CD, Prato M (2005) Biomedical applications of functionalised carbon nanotubes. Chem Commun (Camb) 5:571–577
Li X, Fan Y, Watari F (2010) Current investigations into carbon nanotubes for biomedical application. Biomed Mater 5:22001
Yandar N, Pastorin G, Prato M, Bianco A, Patarroyo ME, Manuel Lozano J (2008) Immunological profile of a Plasmodium vivax AMA-1N-terminus peptide-carbon nanotube conjugate in an infected Plasmodium berghei mouse model. Vaccine 26:5864–5873
Klumpp C, Kostarelos K, Prato M, Bianco A (2006) Functionalized carbon nanotubes as emerging nanovectors for the delivery of therapeutics. Biochim Biophys Acta 1758:404–412
Krajcik R, Jung A, Hirsch A, Neuhuber W, Zolk O (2008) Functionalization of carbon nanotubes enables non-covalent binding and intracellular delivery of small interfering RNA for efficient knock-down of genes. Biochem Biophys Res Commun 369:595–602
Liu Z, Winters M, Holodniy M, Dai H (2007) siRNA delivery into human T cells and primary cells with carbon-nanotube transporters. Angew Chem Int Ed Engl 46:2023–2027
Zhang Z, Yang X, Zhang Y, Zeng B, Wang S, Zhu T, Roden RB, Chen Y, Yang R (2006) Delivery of telomerase reverse transcriptase small interfering RNA in complex with positively charged single-walled carbon nanotubes suppresses tumor growth. Clin Cancer Res 12:4933–4939
Podesta JE, Al-Jamal KT, Herrero MA, Tian B, Ali-Boucetta H, Hegde V, Bianco A, Prato M, Kostarelos K (2009) Antitumor activity and prolonged survival by carbon-nanotube-mediated therapeutic siRNA silencing in a human lung xenograft model. Small 5:1176–1185
Chaudhuri P, Soni S, Sengupta S (2010) Single-walled carbon nanotube-conjugated chemotherapy exhibits increased therapeutic index in melanoma. Nanotechnology 21:025102
Liu Z, Cai W, He L, Nakayama N, Chen K, Sun X, Chen X, Dai H (2007) In vivo biodistribution and highly efficient tumour targeting of carbon nanotubes in mice. Nat Nanotechnol 2:47–52
Teker K (2008) Bioconjugated carbon nanotubes for targeting cancer biomarkers. Mater Sci Eng B 153:83–87
Ji SR, Liu C, Zhang B, Yang F, Xu J, Long J, Jin C, Fu DL, Ni QX, Yu XJ (2010) Carbon nanotubes in cancer diagnosis and therapy. Biochim Biophys Acta 1806:29–35
Bhirde AA, Patel V, Gavard J, Zhang G, Sousa AA, Masedunskas A, Leapman RD, Weigert R, Gutkind JS, Rusling JF (2009) Targeted killing of cancer cells in vivo and in vitro with EGF-directed carbon nanotube-based drug delivery. ACS Nano 3:307–316
Zhang X, Meng L, Lu Q, Fei Z, Dyson PJ (2009) Targeted delivery and controlled release of doxorubicin to cancer cells using modified single wall carbon nanotubes. Biomaterials 30:6041–6047
Wu W, Li R, Bian X, Zhu Z, Ding D, Li X, Jia Z, Jiang X, Hu Y (2009) Covalently combining carbon nanotubes with anticancer agent: preparation and antitumor activity. ACS Nano 3:2740–2750
Frangioni JV (2003) In vivo near-infrared fluorescence imaging. Curr Opin Chem Biol 7:626–634
Marches R, Chakravarty P, Musselman IH, Bajaj P, Azad RN, Pantano P, Draper RK, Vitetta ES (2009) Specific thermal ablation of tumor cells using single-walled carbon nanotubes targeted by covalently-coupled monoclonal antibodies. Int J Cancer 125:2970–2977
Ghosh S, Dutta S, Gomes E, Carroll D, D’Agostino R Jr, Olson J, Guthold M, Gmeiner WH (2009) Increased heating efficiency and selective thermal ablation of malignant tissue with DNA-encased multiwalled carbon nanotubes. ACS Nano 3:2667–2673
De la Zerda A, Zavaleta C, Keren S, Vaithilingam S, Bodapati S, Liu Z, Levi J, Smith BR, Ma TJ, Oralkan O, Cheng Z, Chen X, Dai H, Khuri-Yakub BT, Gambhir SS (2008) Carbon nanotubes as photoacoustic molecular imaging agents in living mice. Nat Nanotechnol 3:557–562
Burke A, Ding X, Singh R, Kraft RA, Levi-Polyachenko N, Rylander MN, Szot C, Buchanan C, Whitney J, Fisher J, Hatcher HC, D’Agostino R Jr, Kock ND, Ajayan PM, Carroll DL, Akman S, Torti FM, Torti SV (2009) Long-term survival following a single treatment of kidney tumors with multiwalled carbon nanotubes and near-infrared radiation. Proc Natl Acad Sci U S A 106:12897–12902
Chakravarty P, Marches R, Zimmerman NS, Swafford AD, Bajaj P, Musselman IH, Pantano P, Draper RK, Vitetta ES (2008) Thermal ablation of tumor cells with antibody-functionalized single-walled carbon nanotubes. Proc Natl Acad Sci U S A 105:8697–8702
Keren S, Zavaleta C, Cheng Z, de la Zerda A, Gheysens O, Gambhir SS (2008) Noninvasive molecular imaging of small living subjects using Raman spectroscopy. Proc Natl Acad Sci U S A 105:5844–5849
Zavaleta C, de la Zerda A, Liu Z, Keren S, Cheng Z, Schipper M, Chen X, Dai H, Gambhir SS (2008) Noninvasive Raman spectroscopy in living mice for evaluation of tumor targeting with carbon nanotubes. Nano Lett 8:2800–2805
Liang F, Chen B (2010) A review on biomedical applications of single-walled carbon nanotubes. Curr Med Chem 17:10–24
Mehra NK, Jain AK, Lodhi N, Raj R, Dubey V, Mishra D, Nahar M, Jain NK (2008) Challenges in the use of carbon nanotubes for biomedical applications. Crit Rev Ther Drug Carrier Syst 25:169–206
Shvedova AA, Kisin ER, Mercer R, Murray AR, Johnson VJ, Potapovich AI, Tyurina YY, Gorelik O, Arepalli S, Schwegler-Berry D, Hubbs AF, Antonini J, Evans DE, Ku BK, Ramsey D, Maynard A, Kagan VE, Castranova V, Baron P (2005) Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon nanotubes in mice. Am J Physiol Lung Cell Mol Physiol 289:L698–L708
Kolosnjaj J, Szwarc H, Moussa F (2007) Toxicity studies of carbon nanotubes. Adv Exp Med Biol 620:181–204
Firme CP, Bandaru PR (2010) Toxicity issues in the application of carbon nanotubes to biological systems. Nanomedicine 6:245–256
Di Sotto A, Chiaretti M, Carru GA, Bellucci S, Mazzanti G (2009) Multi-walled carbon nanotubes: lack of mutagenic activity in the bacterial reverse mutation assay. Toxicol Lett 184:192–197
Monteiro-Riviere NA, Nemanich RJ, Inman AO, Wang YY, Riviere JE (2005) Multi-walled carbon nanotube interactions with human epidermal keratinocytes. Toxicol Lett 155:377–384
Cui D, Tian F, Ozkan CS, Wang M, Gao H (2005) Effect of single wall carbon nanotubes on human HEK293 cells. Toxicol Lett 155:73–85
Manna SK, Sarkar S, Barr J, Wise K, Barrera EV, Jejelowo O, Rice-Ficht AC, Ramesh GT (2005) Single-walled carbon nanotube induces oxidative stress and activates nuclear transcription factor-kappaB in human keratinocytes. Nano Lett 5:1676–1684
Sayes CM, Liang F, Hudson JL, Mendez J, Guo W, Beach JM, Moore VC, Doyle CD, West JL, Billups WE, Ausman KD, Colvin VL (2006) Functionalization density dependence of single-walled carbon nanotubes cytotoxicity in vitro. Toxicol Lett 161:135–142
Bottini M, Bruckner S, Nika K, Bottini N, Bellucci S, Magrini A, Bergamaschi A, Mustelin T (2006) Multi-walled carbon nanotubes induce T lymphocyte apoptosis. Toxicol Lett 160:121–126
Ravichandran P, Baluchamy S, Sadanandan B, Gopikrishnan R, Biradar S, Ramesh V, Hall JC, Ramesh GT (2010) Multiwalled carbon nanotubes activate NF-kappaB and AP-1 signaling pathways to induce apoptosis in rat lung epithelial cells. Apoptosis: an international journal on programmed cell death 15:1507–1516
Patlolla A, Knighten B, Tchounwou P (2010) Multi-walled carbon nanotubes induce cytotoxicity, genotoxicity and apoptosis in normal human dermal fibroblast cells. Ethn Dis 20: S1-65–72
Bai Y, Zhang Y, Zhang J, Mu Q, Zhang W, Butch ER, Snyder SE, Yan B (2010) Repeated administrations of carbon nanotubes in male mice cause reversible testis damage without affecting fertility. Nat Nanotechnol 5:683–689
Sharma CS, Sarkar S, Periyakaruppan A, Barr J, Wise K, Thomas R, Wilson BL, Ramesh GT (2007) Single-walled carbon nanotubes induces oxidative stress in rat lung epithelial cells. J Nanosci Nanotechnol 7:2466–2472
Lam CW, James JT, McCluskey R, Arepalli S, Hunter RL (2006) A review of carbon nanotube toxicity and assessment of potential occupational and environmental health risks. Crit Rev Toxicol 36:189–217
Donaldson K, Aitken R, Tran L, Stone V, Duffin R, Forrest G, Alexander A (2006) Carbon nanotubes: a review of their properties in relation to pulmonary toxicology and workplace safety. Toxicol Sci 92:5–22
Warheit DB, Laurence BR, Reed KL, Roach DH, Reynolds GA, Webb TR (2004) Comparative pulmonary toxicity assessment of single-wall carbon nanotubes in rats. Toxicol Sci 77:117–125
Shvedova AA, Kisin ER, Murray AR, Gorelik O, Arepalli S, Castranova V, Young SH, Gao F, Tyurina YY, Oury TD, Kagan VE (2007) Vitamin E deficiency enhances pulmonary inflammatory response and oxidative stress induced by single-walled carbon nanotubes in C57BL/6 mice. Toxicol Appl Pharmacol 221:339–348
Muller J, Huaux F, Moreau N, Misson P, Heilier JF, Delos M, Arras M, Fonseca A, Nagy JB, Lison D (2005) Respiratory toxicity of multi-wall carbon nanotubes. Toxicol Appl Pharmacol 207:221–231
Kagan VE, Konduru NV, Feng W, Allen BL, Conroy J, Volkov Y, Vlasova II, Belikova NA, Yanamala N, Kapralov A, Tyurina YY, Shi J, Kisin ER, Murray AR, Franks J, Stolz D, Gou P, Klein-Seetharaman J, Fadeel B, Star A, Shvedova AA (2010) Carbon nanotubes degraded by neutrophil myeloperoxidase induce less pulmonary inflammation. Nat Nanotechnol 5:354–359
Folkmann JK, Risom L, Jacobsen NR, Wallin H, Loft S, Moller P (2009) Oxidatively damaged DNA in rats exposed by oral gavage to C60 fullerenes and single-walled carbon nanotubes. Environ Health Perspect 117:703–708
Kolosnjaj-Tabi J, Hartman KB, Boudjemaa S, Ananta JS, Morgant G, Szwarc H, Wilson LJ, Moussa F (2010) In vivo behavior of large doses of ultrashort and full-length single-walled carbon nanotubes after oral and intraperitoneal administration to swiss mice. ACS Nano 4:1481–1492
Ruggiero A, Villa CH, Bander E, Rey DA, Bergkvist M, Batt CA, Manova-Todorova K, Deen WM, Scheinberg DA, McDevitt MR (2010) Paradoxical glomerular filtration of carbon nanotubes. Proc Natl Acad Sci U S A 107:12369–12374
Cherukuri P, Gannon CJ, Leeuw TK, Schmidt HK, Smalley RE, Curley SA, Weisman RB (2006) Mammalian pharmacokinetics of carbon nanotubes using intrinsic near-infrared fluorescence. Proc Natl Acad Sci U S A 103:18882–18886
Zhang D, Deng X, Ji Z, Shen X, Dong L, Wu M, Gu T, Liu Y (2010) Long-term hepatotoxicity of polyethylene-glycol functionalized multi-walled carbon nanotubes in mice. Nanotechnology 21:175101
Poland CA, Duffin R, Kinloch I, Maynard A, Wallace WA, Seaton A, Stone V, Brown S, Macnee W, Donaldson K (2008) Carbon nanotubes introduced into the abdominal cavity of mice show asbestos-like pathogenicity in a pilot study. Nat Nanotechnol 3:423–428
Yang ST, Wang X, Jia G, Gu Y, Wang T, Nie H, Ge C, Wang H, Liu Y (2008) Long-term accumulation and low toxicity of single-walled carbon nanotubes in intravenously exposed mice. Toxicol Lett 181:182–189
Semberova J, De Paoli Lacerda SH, Simakova O, Holada K, Gelderman MP, Simak J (2009) Carbon nanotubes activate blood platelets by inducing extracellular Ca2+ influx sensitive to calcium entry inhibitors. Nano Lett 9:3312–3317
Bihari P, Holzer M, Praetner M, Fent J, Lerchenberger M, Reichel CA, Rehberg M, Lakatos S, Krombach F (2010) Single-walled carbon nanotubes activate platelets and accelerate thrombus formation in the microcirculation. Toxicology 269:148–154
Thompson LC, Frasier CR, Sloan RC, Mann EE, Harrison BS, Brown JM, Brown DA, Wingard CJ (2014) Pulmonary instillation of multi-walled carbon nanotubes promotes coronary vasoconstriction and exacerbates injury in isolated hearts. Nanotoxicology 8:38–49. doi:10.3109/17435390.2012.744858
Stapleton PA, Minarchick VC, Cumpston AM, McKinney W, Chen BT, Sager TM, Frazer DG, Mercer RR, Scabilloni J, Andrew ME, Castranova V, Nurkiewicz TR (2012) Impairment of coronary arteriolar endothelium-dependent dilation after multi-walled carbon nanotube inhalation: a time-course study. Int J Mol Sci 13:13781–13803. doi:10.3390/ijms131113781, ijms131113781 [pii]
Garibaldi S, Brunelli C, Bavastrello V, Ghigliotti G, Nicolini C (2006) Carbon nanotube biocompatibility with cardiac muscle cells. Nanotechnology 17:391–397
Lin Z, Liu L, Xi Z, Huang J, Lin B (2012) Single-walled carbon nanotubes promote rat vascular adventitial fibroblasts to transform into myofibroblasts by SM22-alpha expression. Int J Nanomedicine 7:4199–4206. doi:10.2147/IJN.S34663, ijn-7-4199 [pii]
Martinelli V, Cellot G, Toma FM, Long CS, Caldwell JH, Zentilin L, Giacca M, Turco A, Prato M, Ballerini L, Mestroni L (2012) Carbon nanotubes promote growth and spontaneous electrical activity in cultured cardiac myocytes. Nano Lett 12:1831–1838. doi:10.1021/nl204064s
Zhiqing L, Zhuge X, Fuhuan C, Danfeng Y, Huashan Z, Bencheng L, Wei Z, Huanliang L, Xin S (2010) ICAM-1 and VCAM-1 expression in rat aortic endothelial cells after single-walled carbon nanotube exposure. J Nanosci Nanotechnol 10:8562–8574
Cheng WW, Lin ZQ, Ceng Q, Wei BF, Fan XJ, Zhang HS, Zhang W, Yang HL, Liu HL, Yan J, Tian L, Lin BC, Ding SM, Xi ZG (2012) Single-wall carbon nanotubes induce oxidative stress in rat aortic endothelial cells. Toxicol Mech Methods 22:268–276. doi:10.3109/15376516.2011.647112
Cheng WW, Lin ZQ, Wei BF, Zeng Q, Han B, Wei CX, Fan XJ, Hu CL, Liu LH, Huang JH, Yang X, Xi ZG (2011) Single-walled carbon nanotube induction of rat aortic endothelial cell apoptosis: reactive oxygen species are involved in the mitochondrial pathway. Int J Biochem Cell Biol 43:564–572. doi:10.1016/j.biocel.2010.12.013, S1357-2725(10)00425-5 [pii]
Xu YY, Yang J, Shen T, Zhou F, Xia Y, Fu JY, Meng J, Zhang J, Zheng YF, Xu LH, Zhu XQ (2012) Intravenous administration of multi-walled carbon nanotubes affects the formation of atherosclerosis in Sprague-Dawley rats. J Occup Health 54:361–369, doi:DN/JST.JSTAGE/joh/12-0019-OA [pii]
Cao Y, Jacobsen NR, Danielsen PH, Lenz AG, Stoeger T, Loft S, Wallin H, Roursgaard M, Mikkelsen L, Moller P (2014) Vascular effects of multiwalled carbon nanotubes in dyslipidemic ApoE-/- mice and cultured endothelial cells. Toxicol Sci 138:104–116. doi:10.1093/toxsci/kft328, kft328 [pii]
Ge C, Meng L, Xu L, Bai R, Du J, Zhang L, Li Y, Chang Y, Zhao Y, Chen C (2012) Acute pulmonary and moderate cardiovascular responses of spontaneously hypertensive rats after exposure to single-wall carbon nanotubes. Nanotoxicology 6:526–542. doi:10.3109/17435390.2011.587905
Urankar RN, Lust RM, Mann E, Katwa P, Wang X, Podila R, Hilderbrand SC, Harrison BS, Chen P, Ke PC, Rao AM, Brown JM, Wingard CJ (2012) Expansion of cardiac ischemia/reperfusion injury after instillation of three forms of multi-walled carbon nanotubes. Part Fibre Toxicol 9:38. doi:10.1186/1743-8977-9-38, 1743-8977-9-38 [pii]
Wang B, Feng W, Zhu M, Wang Y, Wang M, Gu Y, Ouyang H, Wang H, Li M, Zhao Y, Chai Z, Wang H (2009) Neurotoxicity of low-dose repeatedly intranasal instillation of nano- and submicron-sized ferric oxide particles in mice. J Nanopart Res 11:41–53
Wang J, Chen C, Liu Y, Jiao F, Li W, Lao F, Li Y, Li B, Ge C, Zhou G, Gao Y, Zhao Y, Chai Z (2008) Potential neurological lesion after nasal instillation of TiO2 nanoparticles in the anatase and rutile crystal phases. Toxicol Lett 183:72–80
Zhang Y, Ali SF, Dervishi E, Xu Y, Li Z, Casciano D, Biris AS (2010) Cytotoxicity effects of graphene and single-wall carbon nanotubes in neural phaeochromocytoma-derived PC12 cells. ACS Nano 4:3181–3186. doi:10.1021/nn1007176
Wang J, Sun P, Bao Y, Liu J, An L (2011) Cytotoxicity of single-walled carbon nanotubes on PC12 cells. Toxicol In Vitro 25:242–250. doi:10.1016/j.tiv.2010.11.010, S0887-2333(10)00302-4 [pii]
Zhang Y, Xu Y, Li Z, Chen T, Lantz SM, Howard PC, Paule MG, Slikker W Jr, Watanabe F, Mustafa T, Biris AS, Ali SF (2011) Mechanistic toxicity evaluation of uncoated and PEGylated single-walled carbon nanotubes in neuronal PC12 cells. ACS Nano 5:7020–7033. doi:10.1021/nn2016259
Wang J, Sun P, Bao Y, Dou B, Song D, Li Y (2012) Vitamin E renders protection to PC12 cells against oxidative damage and apoptosis induced by single-walled carbon nanotubes. Toxicol In Vitro 26:32–41. doi:10.1016/j.tiv.2011.10.004, S0887-2333(11)00270-0 [pii]
Xu H, Bai J, Meng J, Hao W, Cao JM (2009) Multi-walled carbon nanotubes suppress potassium channel activities in PC12 cells. Nanotechnology 20:285102. doi:10.1088/0957-4484/20/28/285102, S0957-4484(09)06963-3 [pii]
Meng L, Chen R, Jiang A, Wang L, Wang P, Li CZ, Bai R, Zhao Y, Autrup H, Chen C (2013) Short multiwall carbon nanotubes promote neuronal differentiation of PC12 cells via up-regulation of the neurotrophin signaling pathway. Small 9:1786–1798. doi:10.1002/smll.201201388
Gavello D, Vandael DH, Cesa R, Premoselli F, Marcantoni A, Cesano F, Scarano D, Fubini B, Carbone E, Fenoglio I, Carabelli V (2012) Altered excitability of cultured chromaffin cells following exposure to multi-walled carbon nanotubes. Nanotoxicology 6:47–60. doi:10.3109/17435390.2011.553294
Varro P, Szigyarto IC, Gergely A, Kalman E, Vilagi I (2013) Carbon nanotubes exert basic excitatory enhancement in rat brain slices. Acta Biol Hung 64:137–151. doi:10.1556/ABiol.64.2013.2.1, 42602421T87W4605 [pii]
Chen T, Yang J, Ren G, Yang Z, Zhang T (2013) Multi-walled carbon nanotube increases the excitability of hippocampal CA1 neurons through inhibition of potassium channels in rat's brain slices. Toxicol Lett 217:121–128. doi:10.1016/j.toxlet.2012.12.013, S0378-4274(12)01442-7 [pii]
Gladwin KM, Whitby RL, Mikhalovsky SV, Tomlins P, Adu J (2013) In vitro biocompatibility of multiwalled carbon nanotubes with sensory neurons. Adv Healthc Mater 2:728–735. doi:10.1002/adhm.201200233
Wu D, Pak ES, Wingard CJ, Murashov AK (2012) Multi-walled carbon nanotubes inhibit regenerative axon growth of dorsal root ganglia neurons of mice. Neurosci Lett 507:72–77. doi:10.1016/j.neulet.2011.11.056, S0304-3940(11)01578-3 [pii]
Han YG, Xu J, Li ZG, Ren GG, Yang Z (2012) In vitro toxicity of multi-walled carbon nanotubes in C6 rat glioma cells. Neurotoxicology 33:1128–1134. doi:10.1016/j.neuro.2012.06.004, S0161-813X(12)00136-2 [pii]
Matsumoto K, Sato C, Naka Y, Whitby R, Shimizu N (2010) Stimulation of neuronal neurite outgrowth using functionalized carbon nanotubes. Nanotechnology 21:115101. doi:10.1088/0957-4484/21/11/115101, S0957-4484(10)37990-6 [pii]
Ivani S, Karimi I, Tabatabaei SR (2012) Biosafety of multiwalled carbon nanotube in mice: a behavioral toxicological approach. J Toxicol Sci 37:1191–1205, doi:DN/JST.JSTAGE/jts/37.1191 [pii]
Bhirde AA, Patel S, Sousa AA, Patel V, Molinolo AA, Ji Y, Leapman RD, Gutkind JS, Rusling JF (2010) Distribution and clearance of PEG-single-walled carbon nanotube cancer drug delivery vehicles in mice. Nanomedicine (Lond) 5:1535–1546. doi:10.2217/nnm.10.90
Wang X, Podila R, Shannahan JH, Rao AM, Brown JM (2013) Intravenously delivered graphene nanosheets and multiwalled carbon nanotubes induce site-specific Th2 inflammatory responses via the IL-33/ST2 axis. Int J Nanomedicine 8:1733–1748. doi:10.2147/IJN.S44211, ijn-8-1733 [pii]
Meng J, Yang M, Jia F, Xu Z, Kong H, Xu H (2011) Immune responses of BALB/c mice to subcutaneously injected multi-walled carbon nanotubes. Nanotoxicology 5:583–591. doi:10.3109/17435390.2010.523483
Sato Y, Yokoyama A, Nodasaka Y, Kohgo T, Motomiya K, Matsumoto H, Nakazawa E, Numata T, Zhang M, Yudasaka M, Hara H, Araki R, Tsukamoto O, Saito H, Kamino T, Watari F, Tohji K (2013) Long-term biopersistence of tangled oxidized carbon nanotubes inside and outside macrophages in rat subcutaneous tissue. Sci Rep 3:2516. doi:10.1038/srep02516, srep02516 [pii]
Pinto NV, de Andrade NF, Martinez DS, Alves OL, Souza Filho AG, Mota MR, Nascimento KS, Cavada BS, Assreuy AM (2013) Inflammatory and hyperalgesic effects of oxidized multi-walled carbon nanotubes in rats. J Nanosci Nanotechnol 13:5276–5282
Trpkovic A, Todorovic-Markovic B, Trajkovic V (2012) Toxicity of pristine versus functionalized fullerenes: mechanisms of cell damage and the role of oxidative stress. Arch Toxicol 86:1809–1827. doi:10.1007/s00204-012-0859-6
Dal Forno GO, Kist LW, de Azevedo MB, Fritsch RS, Pereira TC, Britto RS, Guterres SS, Kulkamp-Guerreiro IC, Bonan CD, Monserrat JM, Bogo MR (2013) Intraperitoneal exposure to nano/microparticles of fullerene (C(6)(0)) increases acetylcholinesterase activity and lipid peroxidation in adult zebrafish (Danio rerio) brain. Biomed Res Int 2013:1–11
Ferreira JL, Lonne MN, Franca TA, Maximilla NR, Lugokenski TH, Costa PG, Fillmann G, Antunes Soares FA, de la Torre FR, Monserrat JM (2014) Co-exposure of the organic nanomaterial fullerene C(6)(0) with benzo[a]pyrene in Danio rerio (zebrafish) hepatocytes: evidence of toxicological interactions. Aquat Toxicol 147:76–83. doi:10.1016/j.aquatox.2013.12.007
Thompson LC, Urankar RN, Holland NA, Vidanapathirana AK, Pitzer JE, Han L, Sumner SJ, Lewin AH, Fennell TR, Lust RM, Brown JM, Wingard CJ (2014) C(6)(0) exposure augments cardiac ischemia/reperfusion injury and coronary artery contraction in Sprague Dawley rats. Toxicol Sci 138:365–378. doi:10.1093/toxsci/kfu008
Goncalves DM, Girard D (2013) Evidence that polyhydroxylated C60 fullerenes (fullerenols) amplify the effect of lipopolysaccharides to induce rapid leukocyte infiltration in vivo. Chem Res Toxicol 26:1884–1892. doi:10.1021/tx4002622
Kalaria DR, Sharma G, Beniwal V, Ravi Kumar MN (2009) Design of biodegradable nanoparticles for oral delivery of doxorubicin: in vivo pharmacokinetics and toxicity studies in rats. Pharm Res 26:492–501
Rytting E, Nguyen J, Wang X, Kissel T (2008) Biodegradable polymeric nanocarriers for pulmonary drug delivery. Expert Opin Drug Deliv 5:629–639
Wilson B, Samanta MK, Santhi K, Kumar KP, Ramasamy M, Suresh B (2010) Chitosan nanoparticles as a new delivery system for the anti-Alzheimer drug tacrine. Nanomedicine 6:144–152
Anand P, Nair HB, Sung B, Kunnumakkara AB, Yadav VR, Tekmal RR, Aggarwal BB (2010) Design of curcumin-loaded PLGA nanoparticles formulation with enhanced cellular uptake, and increased bioactivity in vitro and superior bioavailability in vivo. Biochem Pharmacol 79:330–338
Nanjwade BK, Singh J, Parikh KA, Manvi FV (2010) Preparation and evaluation of carboplatin biodegradable polymeric nanoparticles. Int J Pharm 385:176–180
Jain RA (2000) The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices. Biomaterials 21:2475–2490
Cheng FY, Wang SP, Su CH, Tsai TL, Wu PC, Shieh DB, Chen JH, Hsieh PC, Yeh CS (2008) Stabilizer-free poly(lactide-co-glycolide) nanoparticles for multimodal biomedical probes. Biomaterials 29:2104–2112
Nehilla BJ, Allen PG, Desai TA (2008) Surfactant-free, drug-quantum-dot coloaded poly(lactide-co-glycolide) nanoparticles: towards multifunctional nanoparticles. ACS Nano 2:538–544
Park H, Yang J, Lee J, Haam S, Choi IH, Yoo KH (2009) Multifunctional nanoparticles for combined doxorubicin and photothermal treatments. ACS Nano 3:2919–2926
Betancourt T, Brown B, Brannon-Peppas L (2007) Doxorubicin-loaded PLGA nanoparticles by nanoprecipitation: preparation, characterization and in vitro evaluation. Nanomedicine (Lond) 2:219–232
Dong Y, Feng SS (2007) Poly(D, L-lactide-co-glycolide) (PLGA) nanoparticles prepared by high pressure homogenization for paclitaxel chemotherapy. Int J Pharm 342:208–214
Lee S, Ryu JH, Park K, Lee A, Lee SY, Youn IC, Ahn CH, Yoon SM, Myung SJ, Moon DH, Chen X, Choi K, Kwon IC, Kim K (2009) Polymeric nanoparticle-based activatable near-infrared nanosensor for protease determination in vivo. Nano Lett 9:4412–4416
Myc A, Kukowska-Latallo J, Cao P, Swanson B, Battista J, Dunham T, Baker JR (2010) Targeting the efficacy of a dendrimer-based nanotherapeutic in heterogeneous xenograft tumors in vivo. Anticancer Drugs 21:186–192
Liu M, Fu J, Li J, Wang L, Tan Q, Ren X, Peng Z, Zeng H (2010) Preparation of tri-block copolymer micelles loading novel organoselenium anticancer drug BBSKE and study of tissue distribution of copolymer micelles by imaging in vivo method. Int J Pharm 391:292–304
Xu Y, Wen Z, Xu Z (2009) Chitosan nanoparticles inhibit the growth of human hepatocellular carcinoma xenografts through an antiangiogenic mechanism. Anticancer Res 29:5103–5109
Wang CX, Huang LS, Hou LB, Jiang L, Yan ZT, Wang YL, Chen ZL (2009) Antitumor effects of polysorbate-80 coated gemcitabine polybutylcyanoacrylate nanoparticles in vitro and its pharmacodynamics in vivo on C6 glioma cells of a brain tumor model. Brain Res 1261:91–99
Cenni E, Granchi D, Avnet S, Fotia C, Salerno M, Micieli D, Sarpietro MG, Pignatello R, Castelli F, Baldini N (2008) Biocompatibility of poly(D, L-lactide-co-glycolide) nanoparticles conjugated with alendronate. Biomaterials 29:1400–1411
Kabanov AV (2006) Polymer genomics: an insight into pharmacology and toxicology of nanomedicines. Adv Drug Deliv Rev 58:1597–1621
Kawaguchi T, Honda T, Nishihara M, Yamamoto T, Yokoyama M (2009) Histological study on side effects and tumor targeting of a block copolymer micelle on rats. J Control Release 136:240–246
Chen Z, Chen H, Meng H, Xing G, Gao X, Sun B, Shi X, Yuan H, Zhang C, Liu R, Zhao F, Zhao Y, Fang X (2008) Bio-distribution and metabolic paths of silica coated CdSeS quantum dots. Toxicol Appl Pharmacol 230:364–371
Gao X, Yang L, Petros JA, Marshall FF, Simons JW, Nie S (2005) In vivo molecular and cellular imaging with quantum dots. Curr Opin Biotechnol 16:63–72
Iga AM, Robertson JH, Winslet MC, Seifalian AM (2007) Clinical potential of quantum dots. J Biomed Biotechnol 2007:76087
Cai W, Hsu AR, Li ZB, Chen X (2007) Are quantum dots ready for in vivo imaging in human subjects? Nanoscale Res Lett 2:265–281
Larson DR, Zipfel WR, Williams RM, Clark SW, Bruchez MP, Wise FW, Webb WW (2003) Water-soluble quantum dots for multiphoton fluorescence imaging in vivo. Science 300:1434–1436
Voura EB, Jaiswal JK, Mattoussi H, Simon SM (2004) Tracking metastatic tumor cell extravasation with quantum dot nanocrystals and fluorescence emission-scanning microscopy. Nat Med 10:993–998
Jaiswal JK, Mattoussi H, Mauro JM, Simon SM (2003) Long-term multiple color imaging of live cells using quantum dot bioconjugates. Nat Biotechnol 21:47–51
Schroeder JE, Shweky I, Shmeeda H, Banin U, Gabizon A (2007) Folate-mediated tumor cell uptake of quantum dots entrapped in lipid nanoparticles. J Control Release 124:28–34
Akerman ME, Chan WC, Laakkonen P, Bhatia SN, Ruoslahti E (2002) Nanocrystal targeting in vivo. Proc Natl Acad Sci U S A 99:12617–12621
So MK, Xu C, Loening AM, Gambhir SS, Rao J (2006) Self-illuminating quantum dot conjugates for in vivo imaging. Nat Biotechnol 24:339–343
Al-Jamal WT, Al-Jamal KT, Tian B, Cakebread A, Halket JM, Kostarelos K (2009) Tumor targeting of functionalized quantum dot-liposome hybrids by intravenous administration. Mol Pharm 6:520–530
Pan J, Feng SS (2009) Targeting and imaging cancer cells by folate-decorated, quantum dots (QDs)- loaded nanoparticles of biodegradable polymers. Biomaterials 30:1176–1183
Lin P, Chen JW, Chang LW, Wu JP, Redding L, Chang H, Yeh TK, Yang CS, Tsai MH, Wang HJ, Kuo YC, Yang RS (2008) Computational and ultrastructural toxicology of a nanoparticle, Quantum Dot 705, in mice. Environ Sci Technol 42:6264–6270
Mahto SK, Park C, Yoon TH, Rhee SW (2010) Assessment of cytocompatibility of surface-modified CdSe/ZnSe quantum dots for BALB/3T3 fibroblast cells. Toxicol In Vitro 24:1070–1077
Hardman R (2006) A toxicologic review of quantum dots: toxicity depends on physicochemical and environmental factors. Environ Health Perspect 114:165–172
Wang L, Zheng H, Long Y, Gao M, Hao J, Du J, Mao X, Zhou D (2010) Rapid determination of the toxicity of quantum dots with luminous bacteria. J Hazard Mater 177:1134–1137
Khatchadourian A, Maysinger D (2009) Lipid droplets: their role in nanoparticle-induced oxidative stress. Mol Pharm 6:1125–1137
Hauck TS, Anderson RE, Fischer HC, Newbigging S, Chan WC (2010) In vivo quantum-dot toxicity assessment. Small 6:138–144
Pelley JL, Daar AS, Saner MA (2009) State of academic knowledge on toxicity and biological fate of quantum dots. Toxicol Sci 112:276–296
Lovric J, Cho SJ, Winnik FM, Maysinger D (2005) Unmodified cadmium telluride quantum dots induce reactive oxygen species formation leading to multiple organelle damage and cell death. Chem Biol 12:1227–1234
Cho SJ, Maysinger D, Jain M, Roder B, Hackbarth S, Winnik FM (2007) Long-term exposure to CdTe quantum dots causes functional impairments in live cells. Langmuir 23:1974–1980
Fitzpatrick JA, Andreko SK, Ernst LA, Waggoner AS, Ballou B, Bruchez MP (2009) Long-term persistence and spectral blue shifting of quantum dots in vivo. Nano Lett 9:2736–2741
Geys J, Nemmar A, Verbeken E, Smolders E, Ratoi M, Hoylaerts MF, Nemery B, Hoet PH (2008) Acute toxicity and prothrombotic effects of quantum dots: impact of surface charge. Environ Health Perspect 116:1607–1613
Pons T, Pic E, Lequeux N, Cassette E, Bezdetnaya L, Guillemin F, Marchal F, Dubertret B (2010) Cadmium-free CuInS2/ZnS quantum dots for sentinel lymph node imaging with reduced toxicity. ACS Nano 4:2531–2538
Tseng MT, Lu X, Duan X, Hardas SS, Sultana R, Wu P, Unrine JM, Graham U, Butterfield DA, Grulke EA, Yokel RA (2012) Alteration of hepatic structure and oxidative stress induced by intravenous nanoceria. Toxicol Appl Pharmacol 260:173–182. doi:10.1016/j.taap.2012.02.008
Landsiedel R, Kapp MD, Schulz M, Wiench K, Oesch F (2009) Genotoxicity investigations on nanomaterials: methods, preparation and characterization of test material, potential artifacts and limitations–many questions, some answers. Mutat Res 681:241–258
Manke A, Wang L, Rojanasakul Y (2013) Mechanisms of nanoparticle-induced oxidative stress and toxicity. Biomed Res Int 2013:942916. doi:10.1155/2013/942916
Roesslein M, Hirsch C, Kaiser JP, Krug HF, Wick P (2013) Comparability of in vitro tests for bioactive nanoparticles: a common assay to detect reactive oxygen species as an example. Int J Mol Sci 14:24320–24337. doi:10.3390/ijms141224320
Karlsson HL, Cronholm P, Gustafsson J, Moller L (2008) Copper oxide nanoparticles are highly toxic: a comparison between metal oxide nanoparticles and carbon nanotubes. Chem Res Toxicol 21:1726–1732
He L, Yang L, Zhang ZR, Gong T, Deng L, Gu Z, Sun X (2009) In vitro evaluation of the genotoxicity of a family of novel MeO-PEG-poly(D, L-lactic-co-glycolic acid)-PEG-OMe triblock copolymer and PLGA nanoparticles. Nanotechnology 20:455102
Barnes CA, Elsaesser A, Arkusz J, Smok A, Palus J, Lesniak A, Salvati A, Hanrahan JP, Jong WH, Dziubaltowska E, Stepnik M, Rydzynski K, McKerr G, Lynch I, Dawson KA, Howard CV (2008) Reproducible comet assay of amorphous silica nanoparticles detects no genotoxicity. Nano Lett 8:3069–3074
Jin Y, Kannan S, Wu M, Zhao JX (2007) Toxicity of luminescent silica nanoparticles to living cells. Chem Res Toxicol 20:1126–1133
Shinohara N, Matsumoto K, Endoh S, Maru J, Nakanishi J (2009) In vitro and in vivo genotoxicity tests on fullerene C60 nanoparticles. Toxicol Lett 191:289–296
Mori T, Takada H, Ito S, Matsubayashi K, Miwa N, Sawaguchi T (2006) Preclinical studies on safety of fullerene upon acute oral administration and evaluation for no mutagenesis. Toxicology 225:48–54
Wirnitzer U, Herbold B, Voetz M, Ragot J (2009) Studies on the in vitro genotoxicity of baytubes, agglomerates of engineered multi-walled carbon-nanotubes (MWCNT). Toxicol Lett 186:160–165
Zhu L, Chang DW, Dai L, Hong Y (2007) DNA damage induced by multiwalled carbon nanotubes in mouse embryonic stem cells. Nano Lett 7:3592–3597
Dhawan A, Taurozzi JS, Pandey AK, Shan W, Miller SM, Hashsham SA, Tarabara VV (2006) Stable colloidal dispersions of C60 fullerenes in water: evidence for genotoxicity. Environ Sci Technol 40:7394–7401
Chen M, von Mikecz A (2005) Formation of nucleoplasmic protein aggregates impairs nuclear function in response to SiO2 nanoparticles. Exp Cell Res 305:51–62
AshaRani PV, Low Kah Mun G, Hande MP, Valiyaveettil S (2009) Cytotoxicity and genotoxicity of silver nanoparticles in human cells. ACS Nano 3:279–290
An H, Liu Q, Ji Q, Jin B (2010) DNA binding and aggregation by carbon nanoparticles. Biochem Biophys Res Commun 393:571–576
Park EJ, Yi J, Chung KH, Ryu DY, Choi J, Park K (2008) Oxidative stress and apoptosis induced by titanium dioxide nanoparticles in cultured BEAS-2B cells. Toxicol Lett 180:222–229
Barillet S, Jugan ML, Laye M, Leconte Y, Herlin-Boime N, Reynaud C, Carriere M (2010) In vitro evaluation of SiC nanoparticles impact on A549 pulmonary cells: cyto-, genotoxicity and oxidative stress. Toxicol Lett 198:324–330
Kisin ER, Murray AR, Keane MJ, Shi XC, Schwegler-Berry D, Gorelik O, Arepalli S, Castranova V, Wallace WE, Kagan VE, Shvedova AA (2007) Single-walled carbon nanotubes: geno- and cytotoxic effects in lung fibroblast V79 cells. J Toxicol Environ Health A 70:2071–2079
Muller J, Decordier I, Hoet PH, Lombaert N, Thomassen L, Huaux F, Lison D, Kirsch-Volders M (2008) Clastogenic and aneugenic effects of multi-wall carbon nanotubes in epithelial cells. Carcinogenesis 29:427–433
Huang S, Chueh PJ, Lin YW, Shih TS, Chuang SM (2009) Disturbed mitotic progression and genome segregation are involved in cell transformation mediated by nano-TiO2 long-term exposure. Toxicol Appl Pharmacol 241:182–194
Trouiller B, Reliene R, Westbrook A, Solaimani P, Schiestl RH (2009) Titanium dioxide nanoparticles induce DNA damage and genetic instability in vivo in mice. Cancer Res 69:8784–8789
Hackenberg S, Friehs G, Kessler M, Froelich K, Ginzkey C, Koehler C, Scherzed A, Burghartz M, Kleinsasser N (2011) Nanosized titanium dioxide particles do not induce DNA damage in human peripheral blood lymphocytes. Environ Mol Mutagen 52(4):264–268
Mrdanovic J, Solajic S, Bogdanovic V, Stankov K, Bogdanovic G, Djordjevic A (2009) Effects of fullerenol C60(OH)24 on the frequency of micronuclei and chromosome aberrations in CHO-K1 cells. Mutat Res 680:25–30
Pardridge WM (2005) The blood-brain barrier: bottleneck in brain drug development. NeuroRx 2:3–14
Gao X, Chen J, Chen J, Wu B, Chen H, Jiang X (2008) Quantum dots bearing lectin-functionalized nanoparticles as a platform for in vivo brain imaging. Bioconjug Chem 19:2189–2195
Fernandes C, Soni U, Patravale V (2010) Nano-interventions for neurodegenerative disorders. Pharmacol Res 62:166–178
Kabanov AV, Gendelman HE (2007) Nanomedicine in the diagnosis and therapy of neurodegenerative disorders. Prog Polym Sci 32:1054–1082
Yang H (2010) Nanoparticle-mediated brain-specific drug delivery, imaging, and diagnosis. Pharm Res 27:1759–1771
Gelperina S, Maksimenko O, Khalansky A, Vanchugova L, Shipulo E, Abbasova K, Berdiev R, Wohlfart S, Chepurnova N, Kreuter J (2010) Drug delivery to the brain using surfactant-coated poly(lactide-co-glycolide) nanoparticles: influence of the formulation parameters. Eur J Pharm Biopharm 74:157–163
Wong HL, Chattopadhyay N, Wu XY, Bendayan R (2010) Nanotechnology applications for improved delivery of antiretroviral drugs to the brain. Adv Drug Deliv Rev 62:503–517
Tosi G, Costantino L, Rivasi F, Ruozi B, Leo E, Vergoni AV, Tacchi R, Bertolini A, Vandelli MA, Forni F (2007) Targeting the central nervous system: in vivo experiments with peptide-derivatized nanoparticles loaded with Loperamide and Rhodamine-123. J Control Release 122:1–9
Reimold I, Domke D, Bender J, Seyfried CA, Radunz HE, Fricker G (2008) Delivery of nanoparticles to the brain detected by fluorescence microscopy. Eur J Pharm Biopharm 70:627–632
Oberdorster E (2004) Manufactured nanomaterials (fullerenes, C60) induce oxidative stress in the brain of juvenile largemouth bass. Environ Health Perspect 112:1058–1062
Mistry A, Stolnik S, Illum L (2009) Nanoparticles for direct nose-to-brain delivery of drugs. Int J Pharm 379:146–157
Kreuter J (2004) Influence of the surface properties on nanoparticle-mediated transport of drugs to the brain. J Nanosci Nanotechnol 4:484–488
Steiniger SC, Kreuter J, Khalansky AS, Skidan IN, Bobruskin AI, Smirnova ZS, Severin SE, Uhl R, Kock M, Geiger KD, Gelperina SE (2004) Chemotherapy of glioblastoma in rats using doxorubicin-loaded nanoparticles. Int J Cancer 109:759–767
Alyautdin RN, Petrov VE, Langer K, Berthold A, Kharkevich DA, Kreuter J (1997) Delivery of loperamide across the blood-brain barrier with polysorbate 80-coated polybutylcyanoacrylate nanoparticles. Pharm Res 14:325–328
Kreuter J, Gelperina S (2008) Use of nanoparticles for cerebral cancer. Tumori 94:271–277
Kurakhmaeva KB, Djindjikhashvili IA, Petrov VE, Balabanyan VU, Voronina TA, Trofimov SS, Kreuter J, Gelperina S, Begley D, Alyautdin RN (2009) Brain targeting of nerve growth factor using poly(butyl cyanoacrylate) nanoparticles. J Drug Target 17:564–574
Petri B, Bootz A, Khalansky A, Hekmatara T, Muller R, Uhl R, Kreuter J, Gelperina S (2007) Chemotherapy of brain tumour using doxorubicin bound to surfactant-coated poly(butyl cyanoacrylate) nanoparticles: revisiting the role of surfactants. J Control Release 117:51–58
Sun W, Xie C, Wang H, Hu Y (2004) Specific role of polysorbate 80 coating on the targeting of nanoparticles to the brain. Biomaterials 25:3065–3071
Wilson B, Samanta MK, Santhi K, Kumar KP, Paramakrishnan N, Suresh B (2008) Poly(n-butylcyanoacrylate) nanoparticles coated with polysorbate 80 for the targeted delivery of rivastigmine into the brain to treat Alzheimer's disease. Brain Res 1200:159–168
Mulik RS, Monkkonen J, Juvonen RO, Mahadik KR, Paradkar AR (2010) ApoE3 mediated poly(butyl) cyanoacrylate nanoparticles containing curcumin: study of enhanced activity of curcumin against beta amyloid induced cytotoxicity using in vitro cell culture model. Mol Pharm 7:815–825
Zensi A, Begley D, Pontikis C, Legros C, Mihoreanu L, Wagner S, Buchel C, von Briesen H, Kreuter J (2009) Albumin nanoparticles targeted with Apo E enter the CNS by transcytosis and are delivered to neurones. J Control Release 137:78–86
Tosi G, Vergoni AV, Ruozi B, Bondioli L, Badiali L, Rivasi F, Costantino L, Forni F, Vandelli MA (2010) Sialic acid and glycopeptides conjugated PLGA nanoparticles for central nervous system targeting: in vivo pharmacological evidence and biodistribution. J Control Release 145:49–57
Pandey R, Khuller GK (2006) Oral nanoparticle-based antituberculosis drug delivery to the brain in an experimental model. J Antimicrob Chemother 57:1146–1152
Yang Z, Zhang Y, Yang Y, Sun L, Han D, Li H, Wang C (2010) Pharmacological and toxicological target organelles and safe use of single-walled carbon nanotubes as drug carriers in treating Alzheimer disease. Nanomedicine 6:427–441
Sharma HS, Hussain S, Schlager J, Ali SF, Sharma A (2010) Influence of nanoparticles on blood-brain barrier permeability and brain edema formation in rats. Acta Neurochir Suppl 106:359–364
Win-Shwe TT, Yamamoto S, Fujitani Y, Hirano S, Fujimaki H (2008) Spatial learning and memory function-related gene expression in the hippocampus of mouse exposed to nanoparticle-rich diesel exhaust. Neurotoxicology 29:940–947
Yang Z, Liu ZW, Allaker RP, Reip P, Oxford J, Ahmad Z, Ren G (2010) A review of nanoparticle functionality and toxicity on the central nervous system. J R Soc Interface 7(Suppl 4):S411–S422
Shimizu M, Tainaka H, Oba T, Mizuo K, Umezawa M, Takeda K (2009) Maternal exposure to nanoparticulate titanium dioxide during the prenatal period alters gene expression related to brain development in the mouse. Part Fibre Toxicol 6:20
Rahman MF, Wang J, Patterson TA, Saini UT, Robinson BL, Newport GD, Murdock RC, Schlager JJ, Hussain SM, Ali SF (2009) Expression of genes related to oxidative stress in the mouse brain after exposure to silver-25 nanoparticles. Toxicol Lett 187:15–21
Tang J, Xiong L, Wang S, Wang J, Liu L, Li J, Yuan F, Xi T (2009) Distribution, translocation and accumulation of silver nanoparticles in rats. J Nanosci Nanotechnol 9:4924–4932
Liu J, Hopfinger AJ (2008) Identification of possible sources of nanotoxicity from carbon nanotubes inserted into membrane bilayers using membrane interaction quantitative structure–activity relationship analysis. Chem Res Toxicol 21:459–466. doi:10.1021/tx700392b
Peter C, Hummer G (2005) Ion transport through membrane-spanning nanopores studied by molecular dynamics simulations and continuum electrostatics calculations. Biophys J 89:2222–2234. doi:10.1529/biophysj.105.065946, biophysj.105.065946 [pii]
Shimizu K, Uchiyama A, Yamashita M, Hirose A, Nishimura T, Oku N (2013) Biomembrane damage caused by exposure to multi-walled carbon nanotubes. J Toxicol Sci 38:7–12, doi:DN/JST.JSTAGE/jts/38.7 [pii]
Hirano S, Kanno S, Furuyama A (2008) Multi-walled carbon nanotubes injure the plasma membrane of macrophages. Toxicol Appl Pharmacol 232:244–251. doi:10.1016/j.taap.2008.06.016, S0041-008X(08)00271-8 [pii]
Hirano S, Fujitani Y, Furuyama A, Kanno S (2012) Macrophage receptor with collagenous structure (MARCO) is a dynamic adhesive molecule that enhances uptake of carbon nanotubes by CHO-K1 cells. Toxicol Appl Pharmacol 259:96–103. doi:10.1016/j.taap.2011.12.012, S0041-008X(11)00469-8 [pii]
Shvedova A, Castranova V, Kisin E, Schwegler-Berry D, Murray A, Gandelsman V, Maynard A, Baron P (2003) Exposure to carbon nanotube material: assessment of nanotube cytotoxicity using human keratinocyte cells. J Toxicol Environ Health A 66:1909–1926
Pulskamp K, Diabate S, Krug HF (2007) Carbon nanotubes show no sign of acute toxicity but induce intracellular reactive oxygen species in dependence on contaminants. Toxicol Lett 168:58–74
Fenoglio I, Tomatis M, Lison D, Muller J, Fonseca A, Nagy JB, Fubini B (2006) Reactivity of carbon nanotubes: free radical generation or scavenging activity? Free Radic Biol Med 40:1227–1233. doi:10.1016/j.freeradbiomed.2005.11.010, S0891-5849(05)00708-2 [pii]
Zhu L, Chang DW, Dai L, Hong Y (2007) DNA damage induced by multiwalled carbon nanotubes in mouse embryonic stem cells. Nano Lett 7:3592–3597. doi:10.1021/nl071303v
Pacurari M, Yin XJ, Zhao J, Ding M, Leonard SS, Schwegler-Berry D, Ducatman BS, Sbarra D, Hoover MD, Castranova V, Vallyathan V (2008) Raw single-wall carbon nanotubes induce oxidative stress and activate MAPKs, AP-1, NF-kappaB, and Akt in normal and malignant human mesothelial cells. Environ Health Perspect 116:1211–1217. doi:10.1289/ehp.10924
Choi SJ, Oh JM, Choy JH (2009) Toxicological effects of inorganic nanoparticles on human lung cancer A549 cells. J Inorg Biochem 103:463–471
Pulskamp K (2008) Influence of carbon nanoparticles on cell physiology - mechanistic studies on the toxic effects. Wissenschaftliche Berichte FZKA 7401: A-200
Jia G, Wang H, Yan L, Wang X, Pei R, Yan T, Zhao Y, Guo X (2005) Cytotoxicity of carbon nanomaterials: single-wall nanotube, multi-wall nanotube, and fullerene. Environ Sci Tech 39:1378–1383
Pacurari M, Yin XJ, Ding M, Leonard SS, Schwegler-Berry D, Ducatman BS, Chirila M, Endo M, Castranova V, Vallyathan V (2008) Oxidative and molecular interactions of multi-wall carbon nanotubes (MWCNT) in normal and malignant human mesothelial cells. Nanotoxicology 2:155–170
Sato Y, Shibata K, Kataoka H, Ogino S, Bunshi F, Yokoyama A, Tamura K, Akasaka T, Uo M, Motomiya K, Jeyadevan B, Hatakeyama R, Watari F, Tohji K (2005) Strict preparation and evaluation of water-soluble hat-stacked carbon nanofibers for biomedical application and their high biocompatibility: influence of nanofiber-surface functional groups on cytotoxicity. Mol Biosyst 1:142–145
Sarkar S, Sharma C, Yog R, Periakaruppan A, Jejelowo O, Thomas R, Barrera EV, Rice-Ficht AC, Wilson BL, Ramesh GT (2007) Analysis of stress responsive genes induced by single-walled carbon nanotubes in BJ foreskin cells. J Nanosci Nanotechnol 7:584–592
Witzmann FA, Monteiro-Riviere NA (2006) Multi-walled carbon nanotube exposure alters protein expression in human keratinocytes. Nanomedicine 2:158–168. doi:10.1016/j.nano.2006.07.005, S1549-9634(06)00103-1 [pii]
Barna BP, Huizar I, Malur A, McPeek M, Marshall I, Jacob M, Dobbs L, Kavuru MS, Thomassen MJ (2013) Carbon nanotube-induced pulmonary granulomatous disease: Twist1 and alveolar macrophage M1 activation. Int J Mol Sci 14:23858–23871. doi:10.3390/ijms141223858, ijms141223858 [pii]
Beamer CA, Girtsman TA, Seaver BP, Finsaas KJ, Migliaccio CT, Perry VK, Rottman JB, Smith DE, Holian A (2013) IL-33 mediates multi-walled carbon nanotube (MWCNT)-induced airway hyper-reactivity via the mobilization of innate helper cells in the lung. Nanotoxicology 7:1070–1081. doi:10.3109/17435390.2012.702230
Ronzani C, Spiegelhalter C, Vonesch JL, Lebeau L, Pons F (2012) Lung deposition and toxicological responses evoked by multi-walled carbon nanotubes dispersed in a synthetic lung surfactant in the mouse. Arch Toxicol 86:137–149. doi:10.1007/s00204-011-0741-y
Sager TM, Wolfarth MW, Andrew M, Hubbs A, Friend S, Chen TH, Porter DW, Wu N, Yang F, Hamilton RF, Holian A (2014) Effect of multi-walled carbon nanotube surface modification on bioactivity in the C57BL/6 mouse model. Nanotoxicology 8:317–327. doi:10.3109/17435390.2013.779757
Park EJ, Roh J, Kim SN, Kim Y, Han SB, Hong JT (2013) CCR5 plays an important role in resolving an inflammatory response to single-walled carbon nanotubes. J Appl Toxicol 33:845–853. doi:10.1002/jat.2744
Park EJ, Cho WS, Jeong J, Yi J, Choi K, Park K (2009) Pro-inflammatory and potential allergic responses resulting from B cell activation in mice treated with multi-walled carbon nanotubes by intratracheal instillation. Toxicology 259:113–121
Chang CC, Tsai ML, Huang HC, Chen CY, Dai SX (2012) Epithelial-mesenchymal transition contributes to SWCNT-induced pulmonary fibrosis. Nanotoxicology 6:600–610. doi:10.3109/17435390.2011.594913
Huizar I, Malur A, Patel J, McPeek M, Dobbs L, Wingard C, Barna BP, Thomassen MJ (2013) The role of PPARgamma in carbon nanotube-elicited granulomatous lung inflammation. Respir Res 14:7. doi:10.1186/1465-9921-14-7, 1465-9921-14-7 [pii]
Girtsman TA, Beamer CA, Wu N, Buford M, Holian A (2014) IL-1R signalling is critical for regulation of multi-walled carbon nanotubes-induced acute lung inflammation in C57Bl/6 mice. Nanotoxicology 8:17–27. doi:10.3109/17435390.2012.744110
Di YP, Tkach AV, Yanamala N, Stanley S, Gao S, Shurin MR, Kisin ER, Kagan VE, Shvedova A (2013) Dual acute proinflammatory and antifibrotic pulmonary effects of short palate, lung, and nasal epithelium clone-1 after exposure to carbon nanotubes. Am J Respir Cell Mol Biol 49:759–767. doi:10.1165/rcmb.2012-0435OC
Snyder-Talkington BN, Dymacek J, Porter DW, Wolfarth MG, Mercer RR, Pacurari M, Denvir J, Castranova V, Qian Y, Guo NL (2013) System-based identification of toxicity pathways associated with multi-walled carbon nanotube-induced pathological responses. Toxicol Appl Pharmacol 272:476–489. doi:10.1016/j.taap.2013.06.026, S0041-008X(13)00299-8 [pii]
Snyder-Talkington BN, Pacurari M, Dong C, Leonard SS, Schwegler-Berry D, Castranova V, Qian Y, Guo NL (2013) Systematic analysis of multiwalled carbon nanotube-induced cellular signaling and gene expression in human small airway epithelial cells. Toxicol Sci 133:79–89. doi:10.1093/toxsci/kft019, kft019 [pii]
Tyurina YY, Kisin ER, Murray A, Tyurin VA, Kapralova VI, Sparvero LJ, Amoscato AA, Samhan-Arias AK, Swedin L, Lahesmaa R, Fadeel B, Shvedova AA, Kagan VE (2011) Global phospholipidomics analysis reveals selective pulmonary peroxidation profiles upon inhalation of single-walled carbon nanotubes. ACS Nano 5:7342–7353. doi:10.1021/nn202201j
Wang L, Mercer RR, Rojanasakul Y, Qiu A, Lu Y, Scabilloni JF, Wu N, Castranova V (2010) Direct fibrogenic effects of dispersed single-walled carbon nanotubes on human lung fibroblasts. J Toxicol Environ Health A 73:410–422. doi:10.1080/15287390903486550, 919251280 [pii]
Wang X, Shannahan JH, Brown JM (2014) IL-33 modulates chronic airway resistance changes induced by multi-walled carbon nanotubes. Inhal Toxicol 26:240–249. doi:10.3109/08958378.2014.880202
Wang P, Nie X, Wang Y, Li Y, Ge C, Zhang L, Wang L, Bai R, Chen Z, Zhao Y, Chen C (2013) Multiwall carbon nanotubes mediate macrophage activation and promote pulmonary fibrosis through TGF-beta/Smad signaling pathway. Small 9:3799–3811. doi:10.1002/smll.201300607
Mizutani N, Nabe T, Yoshino S (2012) Exposure to multiwalled carbon nanotubes and allergen promotes early- and late-phase increases in airway resistance in mice. Biol Pharm Bull 35:2133–2140, doi:DN/JST.JSTAGE/bpb/b12-00357 [pii]
Qu C, Wang L, He J, Tan J, Liu W, Zhang S, Zhang C, Wang Z, Jiao S, Liu S, Jiang G (2012) Carbon nanotubes provoke inflammation by inducing the pro-inflammatory genes IL-1beta and IL-6. Gene 493:9–12. doi:10.1016/j.gene.2011.11.046, S0378-1119(11)00716-5 [pii]
Hamilton RF Jr, Buford M, Xiang C, Wu N, Holian A (2012) NLRP3 inflammasome activation in murine alveolar macrophages and related lung pathology is associated with MWCNT nickel contamination. Inhal Toxicol 24:995–1008. doi:10.3109/08958378.2012.745633
Hamilton RF Jr, Xiang C, Li M, Ka I, Yang F, Ma D, Porter DW, Wu N, Holian A (2013) Purification and sidewall functionalization of multiwalled carbon nanotubes and resulting bioactivity in two macrophage models. Inhal Toxicol 25:199–210. doi:10.3109/08958378.2013.775197
Reisetter AC, Stebounova LV, Baltrusaitis J, Powers L, Gupta A, Grassian VH, Monick MM (2011) Induction of inflammasome-dependent pyroptosis by carbon black nanoparticles. J Biol Chem 286:21844–21852. doi:10.1074/jbc.M111.238519, M111.238519 [pii]
Xia T, Hamilton RF, Bonner JC, Crandall ED, Elder A, Fazlollahi F, Girtsman TA, Kim K, Mitra S, Ntim SA, Orr G, Tagmount M, Taylor AJ, Telesca D, Tolic A, Vulpe CD, Walker AJ, Wang X, Witzmann FA, Wu N, Xie Y, Zink JI, Nel A, Holian A (2013) Interlaboratory evaluation of in vitro cytotoxicity and inflammatory responses to engineered nanomaterials: the NIEHS Nano GO Consortium. Environ Health Perspect 121:683–690. doi:10.1289/ehp.1306561
Li R, Wang X, Ji Z, Sun B, Zhang H, Chang CH, Lin S, Meng H, Liao YP, Wang M, Li Z, Hwang AA, Song TB, Xu R, Yang Y, Zink JI, Nel AE, Xia T (2013) Surface charge and cellular processing of covalently functionalized multiwall carbon nanotubes determine pulmonary toxicity. ACS Nano 7:2352–2368. doi:10.1021/nn305567s
Yang M, Flavin K, Kopf I, Radics G, Hearnden CH, McManus GJ, Moran B, Villalta-Cerdas A, Echegoyen LA, Giordani S, Lavelle EC (2013) Functionalization of carbon nanoparticles modulates inflammatory cell recruitment and NLRP3 inflammasome activation. Small 9:4194–4206. doi:10.1002/smll.201300481
Ye S, Jiang Y, Zhang H, Wang Y, Wu Y, Hou Z, Zhang Q (2012) Multi-walled carbon nanotubes induce apoptosis in RAW 264.7 cell-derived osteoclasts through mitochondria-mediated death pathway. J Nanosci Nanotechnol 12:2101–2112
Chen T, Zang J, Wang H, Nie H, Wang X, Shen Z, Tang S, Yang J, Jia G (2012) Water-soluble taurine-functionalized multi-walled carbon nanotubes induce less damage to mitochondria of RAW 264.7 cells. J Nanosci Nanotechnol 12:8008–8016
Wang X, Guo J, Chen T, Nie H, Wang H, Zang J, Cui X, Jia G (2012) Multi-walled carbon nanotubes induce apoptosis via mitochondrial pathway and scavenger receptor. Toxicol In Vitro 26:799–806. doi:10.1016/j.tiv.2012.05.010, S0887-2333(12)00143-9 [pii]
Hamad I, Christy Hunter A, Rutt KJ, Liu Z, Dai H, Moein Moghimi S (2008) Complement activation by PEGylated single-walled carbon nanotubes is independent of C1q and alternative pathway turnover. Mol Immunol 45:3797–3803. doi:10.1016/j.molimm.2008.05.020, S0161-5890(08)00219-8 [pii]
Salvador-Morales C, Basiuk EV, Basiuk VA, Green ML, Sim RB (2008) Effects of covalent functionalization on the biocompatibility characteristics of multi-walled carbon nanotubes. J Nanosci Nanotechnol 8:2347–2356
Salvador-Morales C, Townsend P, Flahaut E, Venien-Bryan C, Vlandas A, Green MLH, Sim RB (2007) Binding of pulmonary surfactant proteins to carbon nanotubes; potential for damage to lung immune defense mechanisms. Carbon 45:607–617
Warheit DB, Donner EM (2010) Rationale of genotoxicity testing of nanomaterials: regulatory requirements and appropriateness of available OECD test guidelines. Nanotoxicology 4:409–413. doi:10.3109/17435390.2010.485704
Belyanskaya L, Manser P, Spohn P, Bruinink A, Wick P (2007) The reliability and limits of the MTT reduction assay for carbon nanotubes-cell interaction. Carbon 45:2643–2648
Casey A, Herzog E, Davoren M, Lyng FM, Byrne HJ, Chambers G (2007) Spectroscopic analysis confirms the interactions between single walled carbon nanotubes and various dyes commonly used to assess cytotoxicity. Carbon 45:1425–1432
Worle-Knirsch JM, Pulskamp K, Krug HF (2006) Oops they did it again! Carbon nanotubes hoax scientists in viability assays. Nano Lett 6:1261–1268
Monteiro-Riviere NA, Inman AO (2006) Challenges for assessing carbon nanomaterial toxicity to the skin. Carbon 44:1070–1078
Davoren M, Herzog E, Casey A, Cottineau B, Chambers G, Byrne HJ, Lyng FM (2007) In vitro toxicity evaluation of single walled carbon nanotubes on human A549 lung cells. Toxicol In Vitro 21:438–448
Li X, Gao H, Uo M, Sato Y, Akasaka T, Abe S, Feng Q, Cui F, Watari F (2008) Maturation of osteoblast-like SaoS2 induced by carbon nanotubes. Biomed Mater 4:15005. doi:10.1088/1748-6041/4/1/015005, S1748-6041(09)85639-8 [pii]
Li X, Gao H, Uo M, Sato Y, Akasaka T, Feng Q, Cui F, Liu X, Watari F (2008) Effect of carbon nanotubes on cellular functions in vitro. J Biomed Mater Res A. doi:10.1002/jbm.a.32203
Cherukuri P, Gannon CJ, Leeuw TK, Schmidt HK, Smalley RE, Curley SA, Weisman RB (2006) Mammalian pharmacokinetics of carbon nanotubes using intrinsic near-infrared fluorescence. Proc Natl Acad Sci U S A 103:18882–18886. doi:10.1073/pnas.0609265103
Chen J, Chen W, Zhu D (2008) Adsorption of nonionic aromatic compounds to single-walled carbon nanotubes: effects of aqueous solution chemistry. Environ Sci Tech 42:7225–7230. doi:10.1021/es801412j
Lin D, Xing B (2008) Adsorption of phenolic compounds by carbon nanotubes: role of aromaticity and substitution of hydroxyl groups. Environ Sci Tech 42:7254–7259. doi:10.1021/es801297u
Yang K, Zhu L, Xing B (2006) Adsorption of polycyclic aromatic hydrocarbons by carbon nanomaterials. Environ Sci Tech 40:1855–1861. doi:10.1021/es052208w
Yang K, Wu W, Jing Q, Zhu L (2008) Aqueous adsorption of aniline, phenol, and their substitutes by multi-walled carbon nanotubes. Environ Sci Tech 42:7931–7936. doi:10.1021/es801463v
Guo L, Von Dem Bussche A, Buechner M, Yan A, Kane AB, Hurt RH (2008) Adsorption of essential micronutrients by carbon nanotubes and the implications for nanotoxicity testing. Small 4:721–727. doi:10.1002/smll.200700754
Casey A, Davoren M, Herzog E, Lyng FM, Byrne HJ, Chambers G (2007) Probing the interaction of single walled carbon nanotubes within cell culture medium as a precursor to toxicity testing. Carbon 45:34–40
Casey A, Herzog E, Lyng FM, Byrne HJ, Chambers G, Davoren M (2008) Single walled carbon nanotubes induce indirect cytotoxicity by medium depletion in A549 lung cells. Toxicol Lett 179:78–84. doi:10.1016/j.toxlet.2008.04.006, S0378-4274(08)00107-0 [pii]
Kapralov AA, Feng WH, Amoscato AA, Yanamala N, Balasubramanian K, Winnica DE, Kisin ER, Kotchey GP, Gou P, Sparvero LJ, Ray P, Mallampalli RK, Klein-Seetharaman J, Fadeel B, Star A, Shvedova AA, Kagan VE (2012) Adsorption of surfactant lipids by single-walled carbon nanotubes in mouse lung upon pharyngeal aspiration. ACS Nano 6:4147–4156. doi:10.1021/nn300626q
Wang L, Castranova V, Mishra A, Chen B, Mercer RR, Schwegler-Berry D, Rojanasakul Y (2010) Dispersion of single-walled carbon nanotubes by a natural lung surfactant for pulmonary in vitro and in vivo toxicity studies. Part Fibre Toxicol 7:31. doi:10.1186/1743-8977-7-31, 1743-8977-7-31 [pii]
Fadel TR, Look M, Staffier PA, Haller GL, Pfefferle LD, Fahmy TM (2010) Clustering of stimuli on single-walled carbon nanotube bundles enhances cellular activation. Langmuir 26:5645–5654. doi:10.1021/la902068z
Li X, Gao H, Uo M, Sato Y, Akasaka T, Feng Q, Cui F, Liu X, Watari F (2009) Effect of carbon nanotubes on cellular functions in vitro. J Biomed Mater Res A 91:132–139. doi:10.1002/jbm.a.32203
Li X, Liu H, Niu X, Yu B, Fan Y, Feng Q, Cui FZ, Watari F (2012) The use of carbon nanotubes to induce osteogenic differentiation of human adipose-derived MSCs in vitro and ectopic bone formation in vivo. Biomaterials 33:4818–4827. doi:10.1016/j.biomaterials.2012.03.045, S0142-9612(12)00332-8 [pii]
Adamopoulos IE, Abstracts tSRMotACS, Little Rock, AR, United States, October 1–4 FIELD Full Journal Title:Abstracts, 64th Southwest Regional Meeting of the American Chemical Society, Little Rock, AR, United States, Duffin R, Mills Nicholas L, Donaldson K (2007) Nanoparticles-a thoracic toxicology perspective. Yonsei Med J 48:561–572
Liu X, Guo L, Morris D, Kane AB, Hurt RH (2008) Targeted removal of bioavailable metal as a detoxification strategy for carbon nanotubes. Carbon N Y 46:489–500
Kagan VE, Tyurina YY, Tyurin VA, Konduru NV, Potapovich AI, Osipov AN, Kisin ER, Schwegler-Berry D, Mercer R, Castranova V, Shvedova AA (2006) Direct and indirect effects of single walled carbon nanotubes on RAW 264.7 macrophages: role of iron. Toxicol Lett 165:88–100
Pensabene V, Vittorio O, Raffa V, Menciassi A, Dario P (2007) Investigation of CNTs interaction with fibroblast cells. In: Conference proceedings of IEEE engineering in medicine and biology society, vol 2007, pp. 6621–6624. doi:10.1109/IEMBS.2007.4353877
Gavello D, Fenoglio I, Fubini B, Cesano F, Premoselli F, Renna A, Carbone E, Carabelli V (2013) Inhibition of catecholamine secretion by iron-rich and iron-deprived multiwalled carbon nanotubes in chromaffin cells. Neurotoxicology 39:84–94. doi:10.1016/j.neuro.2013.08.008, S0161-813X(13)00132-0 [pii]
Meng L, Jiang A, Chen R, Li CZ, Wang L, Qu Y, Wang P, Zhao Y, Chen C (2013) Inhibitory effects of multiwall carbon nanotubes with high iron impurity on viability and neuronal differentiation in cultured PC12 cells. Toxicology 313:49–58. doi:10.1016/j.tox.2012.11.011, S0300-483X(12)00408-8 [pii]
Crouzier T, Nimmagadda A, Nollert MU, McFetridge PS (2008) Modification of single walled carbon nanotube surface chemistry to improve aqueous solubility and enhance cellular interactions. Langmuir 24:13173–13181. doi:10.1021/la801999n
Simon-Deckers A, Gouget B, Mayne-L'Hermite M, Herlin-Boime N, Reynaud C, Carriere M (2008) In vitro investigation of oxide toxicity and intracellular accumulation in A549 human pneumocytes. Toxicology 253:137–146
Jin H, Heller DA, Sharma R, Strano MS (2009) Size-dependent cellular uptake and expulsion of single-walled carbon nanotubes: single particle tracking and a generic uptake model for nanoparticles. ACS Nano 3:149–158
Nicola MD, Bellucci S, Traversa E, Bellis GD, Micciulla F, Ghibelli L (2008) Carbon nanotubes on Jurkat cells: effects on cell viability and plasma membrane potential. J Phys Condens Matter 20:474204
Sato Y, Yokoyama A, Shibata K, Akimoto Y, Ogino S, Nodasaka Y, Kohgo T, Tamura K, Akasaka T, Uo M, Motomiya K, Jeyadevan B, Ishiguro M, Hatakeyama R, Watari F, Tohji K (2005) Influence of length on cytotoxicity of multi-walled carbon nanotubes against human acute monocytic leukemia cell line THP-1 in vitro and subcutaneous tissue of rats in vivo. Mol Biosyst 1:176–182
Tohji K, Sato Y (2006) Influence of purity and morphology on tissue reactivity of carbon nanotubes. Baiomateriaru 24:333–344
Simon-Deckers A, Gouget B, Mayne-L'hermite M, Herlin-Boime N, Reynaud C, Carriere M (2008) In vitro investigation of oxide nanoparticle and carbon nanotube toxicity and intracellular accumulation in A549 human pneumocytes. Toxicology 253:137–146
Wick P, Manser P, Limbach LK, Dettlaff-Weglikowska U, Krumeich F, Roth S, Stark WJ, Bruinink A (2007) The degree and kind of agglomeration affect carbon nanotube cytotoxicity. Toxicol Lett 168:121–131
Elgrabli D, Abella-Gallart S, Aguerre-Chariol O, Robidel F, Rogerieux F, Boczkowski J, Lacroix G (2007) Effect of BSA on carbon nanotube dispersion for in vivo and in vitro studies. Nanotoxicology 1:266–278
Moore VC, Leonard A, Price BK, Conyers JL, Tour JM (2007) The effect of physical characteristics on biocompatibility and cellular internalization of carbon nanotubes. In: 233rd ACS national meeting, Chicago, IL, United States, pp. INOR-531
Wu P, Chen X, Hu N, Tam UC, Blixt O, Zettl A, Bertozzi CR (2008) Biocompatible carbon nanotubes generated by functionalization with glycodendrimers. Angewandte Chemie 47:5022–5025
Fadel TR, Steenblock ER, Stern E, Li N, Wang X, Haller GL, Pfefferle LD, Fahmy TM (2008) Enhanced cellular activation with single walled carbon nanotube bundles presenting antibody stimuli. Nano Lett 8:2070–2076. doi:10.1021/nl080332i
Prencipe G, Tabakman SM, Welsher K, Liu Z, Goodwin AP, Zhang L, Henry J, Dai H (2009) PEG branched polymer for functionalization of nanomaterials with ultralong blood circulation. J Am Chem Soc 131(13):4783–4787
Li J, Xue Y, Han B, Li Q, Liu L, Xiao T, Li W (2008) Application of X-ray phase contrast imaging technique in detection of pulmonary lesions induced by multi-walled carbon nanotubes in rats. J Nanosci Nanotechnol 8:3357–3362
Al Faraj A, Cieslar K, Lacroix G, Gaillard S, Canet-Soulas E, Cremillieux Y (2009) In vivo imaging of carbon nanotube biodistribution using magnetic resonance imaging. Nano Lett 9(3):1023–1027
Lacerda L, Soundararajan A, Singh R, Pastorin G, Al-Jamal KT, Turton J, Frederik P, Herrero MA, Li S, Bao A, Emfietzoglou D, Mather S, Phillips WT, Prato M, Bianco A, Goins B, Kostarelos K (2008) Dynamic imaging of functionalized multi-walled carbon nanotube systemic circulation and urinary excretion. Adv Mater 20:225–230
Bussy C, Cambedouzou J, Lanone S, Leccia E, Heresanu V, Pinault M, Mayne-L'hermite M, Brun N, Mory C, Cotte M, Doucet J, Boczkowski J, Launois P (2008) Carbon nanotubes in macrophages: imaging and chemical analysis by X-ray fluorescence microscopy. Nano Lett 8:2659–2663. doi:10.1021/nl800914m
Jin H, Heller DA, Strano MS (2008) Single-particle tracking of endocytosis and exocytosis of single-walled carbon nanotubes in NIH-3T3 cells. Nano Lett 8:1577–1585
Liu Z, Li X, Tabakman SM, Jiang K, Fan S, Dai H (2008) Multiplexed multicolor Raman imaging of live cells with isotopically modified single walled carbon nanotubes. J Am Chem Soc 130:13540–13541
Herzog E, Casey A, Lyng FM, Chambers G, Byrne HJ, Davoren M (2007) A new approach to the toxicity testing of carbon-based nanomaterials-the clonogenic assay. Toxicol Lett 174:49–60
Zhou H, Mu Q, Gao N, Liu A, Xing Y, Gao S, Zhang Q, Qu G, Chen Y, Liu G, Zhang B, Yan B (2008) A nano-combinatorial library strategy for the discovery of nanotubes with reduced protein-binding, cytotoxicity, and immune response. Nano Lett 8:859–865
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Controlled Release Society
About this chapter
Cite this chapter
Godugu, C., Singh, R.P., Poduri, R. (2015). Nanotoxicology: Contemporary Issues and Future Directions. In: Devarajan, P., Jain, S. (eds) Targeted Drug Delivery : Concepts and Design. Advances in Delivery Science and Technology. Springer, Cham. https://doi.org/10.1007/978-3-319-11355-5_23
Download citation
DOI: https://doi.org/10.1007/978-3-319-11355-5_23
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-11354-8
Online ISBN: 978-3-319-11355-5
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)