Skip to main content
SpringerLink
Log in

Do Nanomedicines Require Novel Safety Assessments to Ensure their Safety for Long-Term Human Use?

  • Current Opinion
  • Published:
Drug Safety Aims and scope Submit manuscript

Abstract

Nanomaterials have different chemical, physical and biological characteristics than larger materials of the same chemical composition. These differences give nanotechnology a double identity: their use implies novel and interesting medical and/or industrial applications but also potential danger for human and environmental health. Here, we briefly review the most important types of nanomaterials, the difficulties in assessing safety or toxicity, and describe existing test protocols used in nanomaterial safety evaluation. In general, the big challenge of nanotechnology, particularly for nanomedicine (nanobioengineering), is to understand which nano-specific characteristics interact with particular biological systems and functions in order to optimize the therapeutic potential and reduce the undesired responses. The evaluation of the safety of medicinal nanomaterials, especially for long-term application, is an important challenge for the near future. At present, it is still too early to predict, on the basis of the characteristics of the nanomaterial, a possible biological response because no reliable database exists. Therefore, a case-by-case approach for hazard identification is still required, so it is difficult to establish a risk assessment framework.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Oberdorster G, Oberdorster E, Oberdorster J. Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 2005; 113(7): 823–39

    Article  PubMed  CAS  Google Scholar 

  2. Maynard AD, Aitken RJ, Butz T, et al. Safe handling of nanotechnology. Nature 2006; 444(7117): 267–9

    Article  PubMed  CAS  Google Scholar 

  3. The Royal Society & The Royal Academy of Engineering. Nanoscience and nanotechnologies: opportunities and uncertainties. Summary and recommendations [online]. Available from URL: http://www.nanotec.org.uk/finalReport.htm [Accessed 2009 May 29]

  4. Caruthers SD, Wickline SA, Lanza GM. Nanotechnological applications in medicine. Curr Opin Biotechnol 2007; 18(1): 26–30

    Article  PubMed  CAS  Google Scholar 

  5. Leroueil PR, Hong S, Mecke A, et al. Nanoparticle interaction with biological membranes: does nanotechnology present a Janus face? Acc Chem Res 2007; 40(5): 335–42

    Article  PubMed  CAS  Google Scholar 

  6. Donaldson K, Seaton A. The Janus faces of nanoparticles. J Nanosci Nanotechnol 2007; 7(12): 4607–11

    PubMed  CAS  Google Scholar 

  7. Warheit DB, Borm PJ, Hennes C, et al. Testing strategies to establish the safety of nanomaterials: conclusions of an ECETOC workshop. Inhal Toxicol 2007; 19(8): 631–43

    Article  PubMed  CAS  Google Scholar 

  8. Medina C, Santos-Martinez MJ, Radomski A, et al. Nanoparticles: pharmacological and toxicological significance. Br J Pharmacol 2007; 150(5): 552–8

    Article  PubMed  CAS  Google Scholar 

  9. Sarker DK. Engineering of nanoemulsions for drug delivery. Curr Drug Deliv 2005; 2(4): 297–310

    Article  PubMed  CAS  Google Scholar 

  10. Agnihotri SA, Mallikarjuna NN, Aminabhavi TM. Recent advances on chitosan-based micro- and nanoparticles in drug delivery. J Control Release 2004; 100(1): 5–28

    Article  PubMed  CAS  Google Scholar 

  11. Cherian AK, Rana AC, Jain SK. Self-assembled carbohydrate-stabilized ceramic nanoparticles for the parenteral delivery of insulin. Drug Dev Ind Pharm 2000; 26(4): 459–63

    Article  PubMed  CAS  Google Scholar 

  12. Yamamoto A, Honma R, Sumita M, et al. Cytotoxicity evaluation of ceramic particles of different sizes and shapes. J Biomed Mater Res A 2004; 68(2): 244–56

    Article  PubMed  CAS  Google Scholar 

  13. Gupta AK, Naregalkar RR, Vaidya VD, et al. Recent advances on surface engineering of magnetic iron oxide nanoparticles and their biomedical applications. Nanomed 2007; 2(1): 23–39

    Article  CAS  Google Scholar 

  14. Weng J, Ren J. Luminescent quantum dots: a very attractive and promising tool in biomedicine. Curr Med Chem 2006; 13(8): 897–909

    Article  PubMed  CAS  Google Scholar 

  15. Hirsch LR, Gobin AM, Lowery AR, et al. Metal nanoshells. Ann Biomed Eng 2006; 34(1): 15–22

    Article  PubMed  Google Scholar 

  16. Prato M, Kostarelos K, Bianco A. Functionalized carbon nanotubes in drug design and discovery. Acc Chem Res 2008; 41(1): 60–8

    Article  PubMed  CAS  Google Scholar 

  17. Lam CW, James JT, McCluskey R, et al. A review of carbon nanotube toxicity and assessment of potential occupational and environmental health risks. Crit Rev Toxicol 2006; 36(3): 189–217

    Article  PubMed  CAS  Google Scholar 

  18. Murakami T, Tsuchida K. Recent advances in inorganic nanoparticle-based drug delivery systems. Mini Rev Med Chem 2008; 8(2): 175–83

    Article  PubMed  CAS  Google Scholar 

  19. Reasor MJ, Hastings KL, Ulrich RG. Drug-induced phospholipidosis: issues and future directions. Expert Opin Drug Saf 2006; 5(4): 567–83

    Article  PubMed  CAS  Google Scholar 

  20. ICH. Note for guidance on preclinical safety evaluation of biotechnology-derived pharmaceuticals. ICH topic: preclinical safety evaluation of biotechnology-derived pharmaceuticals. London: EMEA, 1998; S6: 1–10

    Google Scholar 

  21. Fabian E, Landsiedel R, Ma-Hock L, et al. Tissue distribution and toxicity of intravenously administered titanium dioxide nanoparticles in rats. Arch Toxicol 2008; 82(3): 151–7

    Article  PubMed  CAS  Google Scholar 

  22. Worle-Knirsch JM, Pulskamp K, Krug HF. Oops they did it again! Carbon nanotubes hoax scientists in viability assays. Nano Lett 2006; 6(6): 1261–8

    Article  PubMed  CAS  Google Scholar 

  23. Pulskamp K, Diabaté S, Krug HF. Carbon nanotubes show no sign of acute toxicity but induce intracellular reactive oxygen species in dependence on contaminants. Toxicol Lett 2007; 1(4): 293–9

    Google Scholar 

  24. Cui D, Tian F, Ozkan CS, et al. Effect of single wall carbon nanotubes on human HEK293 cells. Toxicol Lett 2005; 155: 73–85

    Article  PubMed  CAS  Google Scholar 

  25. Murr LE, Garza KM, Soto KF, et al. Cytotoxicity assessment of some carbon nanotubes and related carbon nanoparticle aggregates and the implications for anthropogenic carbon nanotube aggregates in the environment. Int J Environ Res Public Health 2005; 2(1): 31–42

    Article  PubMed  CAS  Google Scholar 

  26. Soto KF, Carrasco A, Powell TG, et al. Comparative in vitro cytotoxicity assessment of some manufactured nanoparticulate materials characterized by transmission electron microscopy. J Nanopart Res 2005; 7: 145–69

    Article  CAS  Google Scholar 

  27. Soto K, Garza KM, Murr LE. Cytotoxic effects of aggregated nanomaterials. Acta Biomater 2007; 3(3): 351–8

    Article  PubMed  CAS  Google Scholar 

  28. Sayes CM, Wahi R, Kurian PA, et al. Correlating nanoscale titania structure with toxicity: a cytotoxicity and inflammatory response study with human dermal fibroblasts and human lung epithelial cells. Toxicol Sci 2006; 92(1): 174–85

    Article  PubMed  CAS  Google Scholar 

  29. Zhang LW, Zeng L, Barron AR, et al. Biological interactions of functionalized single-wall carbon nanotubes in human epidermal keratinocytes. Int J Toxicol 2007; 26(2): 103–13

    Article  PubMed  CAS  Google Scholar 

  30. Dutta D, Sundaram SK, Teeguarden JG, et al. Adsorbed proteins influence the biological activity and molecular targeting of nanomaterials. Toxicol Sci 2007; 100(1): 303–15

    Article  PubMed  CAS  Google Scholar 

  31. Schimmelpfeng J, Drosselmeyer E, Hofheinz V, et al. Influence of surfactant components and exposure geometry on the effects of quartz and asbestos on alveolar macrophages. Environ Health Perspect 1992; 97: 225–31

    Article  PubMed  CAS  Google Scholar 

  32. Gao N, Keane MJ, Ong T, et al. Effects of phospholipid surfactant on apoptosis induction by respirable quartz and kaolin in NR8383 rat pulmonary macrophages. Toxicol Appl Pharmacol 2001; 175(3): 217–25

    Article  PubMed  CAS  Google Scholar 

  33. Wallace WE, Keane MJ, Murray DK, et al. Phospholipid lung surfactant and nanoparticle surface toxicity: lessons from diesel soots and silicate dusts. J Nanopart Res 2007; 9: 23–38

    Article  CAS  Google Scholar 

  34. Monteiro-Riviere NA, Nemanich RJ, Inman AO, et al. Multi-walled carbon nanotube interactions with human epidermal keratinocytes. Toxicol Lett 2005; 155: 377–84

    Article  PubMed  CAS  Google Scholar 

  35. Davoren M, Herzog E, Casey A, et al. In vitro toxicity evaluation of single walled carbon nanotubes on human A549 lung cells. Toxicol In Vitro 2007; 21: 438–48

    Article  PubMed  CAS  Google Scholar 

  36. Wick P, Manser P, Limbach LK, et al. The degree and kind of agglomeration affect carbon nanotube cytotoxicity. Toxicol Lett 2007; 168(2): 121–31

    Article  PubMed  CAS  Google Scholar 

  37. Smart SK, Cassady AI, Lu GQ, et al. The biocompatibility of carbon nanotubes. Carbon 2006; 44: 1034–47

    Article  CAS  Google Scholar 

  38. Murdock RC, Braydich-Stolle L, Schrand AM, et al. Characterization of nanomaterial dispersion in solution prior to in vitro exposure using dynamic light scattering technique. Toxicol Sci 2007; 101(2): 239–53

    Article  PubMed  CAS  Google Scholar 

  39. Monteiro-Riviere NA, Inman AO. Challenges for assessing carbon nanomaterial toxicity to the skin. Carbon 2006; 44: 1070–8

    Article  CAS  Google Scholar 

  40. Hurt RH, Monthioux M, Kane A. Toxicology of carbon nanomaterials: status, trends, and perspectives on the special issue. Carbon 2006; 44: 1028–33

    Article  CAS  Google Scholar 

  41. Hoet PH, Bruske-Hohlfeld I, Salata OV. Nanoparticles: known and unknown health risks. J Nanobiotechnol 2004; 2(1): 12

    Article  CAS  Google Scholar 

  42. Oberdörster G, Ferin J, Lehnert BE. Correlation between particle size, in vivo particle persistence, and lung injury. Environ Health Perspect 1994; 102 Suppl. 5: 173–9

    Article  PubMed  Google Scholar 

  43. Nemmar A, Hoet PH, Vanquickenborne B, et al. Passage of inhaled particles into the blood circulation in humans. Circulation 2002; 105(4): 411–4

    Article  PubMed  CAS  Google Scholar 

  44. Nemmar A, Vanbilloen H, Hoylaerts MF, et al. Passage of intratracheally instilled ultrafine particles from the lung into the systemic circulation in hamster. Am J Respir Crit Care Med 2001; 164(9): 1665–8

    PubMed  CAS  Google Scholar 

  45. Kreyling WG, Semmler M, Erbe F, et al. Translocation of ultrafine insoluble iridium particles from lung epithelium to extrapulmonary organs is size dependent but very low. J Toxicol Environ Health A 2002; 65(20): 1513–30

    Article  PubMed  CAS  Google Scholar 

  46. Rothen-Rutishauser B, Muhlfeld C, Blank F, et al. Translocation of particles and inflammatory responses after exposure to fine particles and nanoparticles in an epithelial airway model. Part Fibre Toxicol 2007; 4: 9

    Article  PubMed  CAS  Google Scholar 

  47. Muhlfeld C, Mayhew TM, Gehr P, et al. A novel quantitative method for analyzing the distributions of nanoparticles between different tissue and intracellular compartments. J Aerosol Med 2007; 20(4): 395–407

    Article  PubMed  CAS  Google Scholar 

  48. Kling J. Inhaled insulin’s last gasp? Nat Biotechnol 2008; 26(5): 479–80

    Article  PubMed  CAS  Google Scholar 

  49. Kreilgaard M. Influence of microemulsions on cutaneous drug delivery. Adv Drug Deliv Rev 2002; 54 Suppl. 1: S77–98

    Article  PubMed  CAS  Google Scholar 

  50. Ryman-Rasmussen JP, Riviere JE, Monteiro-Riviere NA. Penetration of intact skin by quantum dots with diverse physicochemical properties. Toxicol Sci 2006; 91(1): 159–65

    Article  PubMed  CAS  Google Scholar 

  51. Jani P, Halbert GW, Langridge J, et al. Nanoparticle uptake by the rat gastrointestinal mucosa: quantitation and particle size dependency. J Pharm Pharmacol 1990; 42(12): 821–6

    Article  PubMed  CAS  Google Scholar 

  52. Yamago S, Tokuyama H, Nakamura E, et al. In vivo biological behavior of a water-miscible fullerene: 14C labeling, absorption, distribution, excretion and acute toxicity. Chem Biol 1995; 2(6): 385–9

    Article  PubMed  CAS  Google Scholar 

  53. Qu X, Khutoryanskiy VV, Stewart A, et al. Carbohydrate-based micelle clusters which enhance hydrophobic drug bioavailability by up to 1 order of magnitude. Biomacromolecules 2006; 7(12): 3452–9

    Article  PubMed  CAS  Google Scholar 

  54. Brown JS, Zeman KL, Bennett WD. Ultrafine particle deposition and clearance in the healthy and obstructed lung. Am J Respir Crit Care Med 2002; 166(9): 1240–7

    Article  PubMed  Google Scholar 

  55. Takenaka S, Karg E, Roth C, et al. Pulmonary and systemic distribution of inhaled ultrafine silver particles in rats. Environ Health Perspect 2001; 109 Suppl. 4: 547–51

    Article  PubMed  CAS  Google Scholar 

  56. Nigavekar SS, Sung LY, Llanes M, et al. 3H Dendrimer nanoparticle organ/tumor distribution. Pharm Res 2004; 21(3): 476–83

    Article  PubMed  CAS  Google Scholar 

  57. Sayes CM, Liang F, Hudson JL, et al. Functionalization density dependence of single-walled carbon nanotubes cytotoxicity in vitro. Toxicol Lett 2006; 161(2): 135–42

    Article  PubMed  CAS  Google Scholar 

  58. Warheit DB, Webb TR, Reed KL, et al. Pulmonary toxicity study in rats with three forms of ultrafine-TiO2 particles: differential responses related to surface properties. Toxicology 2007; 230(1): 90–104

    Article  PubMed  CAS  Google Scholar 

  59. Warheit DB, Brock WJ, Lee KP, et al. Comparative pulmonary toxicity inhalation and instillation studies with different TiO2 particle formulations: impact of surface treatments on particle toxicity. Toxicol Sci 2005; 88(2): 514–24

    Article  PubMed  CAS  Google Scholar 

  60. Lomer MC, Hutchinson C, Volkert S, et al. Dietary sources of inorganic microparticles and their intake in healthy subjects and patients with Crohn’s disease. Br J Nutr 2004; 92(6): 947–55

    Article  PubMed  CAS  Google Scholar 

  61. Florence AT. Issues in oral nanoparticle drug carrier uptake and targeting. J Drug Target 2004; 12(2): 65–70

    Article  PubMed  CAS  Google Scholar 

  62. ICH. Note for guidance on the genotoxicity testing and data interpretation for pharmaceuticals intended for human use. ICH topic: preclinical safety evaluation of biotechnologyderived pharmaceuticals. London: EMEA, 2008; S2: 1–28

    Google Scholar 

  63. Schins RP, Knaapen AM. Genotoxicity of poorly soluble particles. Inhal Toxicol 2007; 19 Suppl. 1: 189–98

    Article  PubMed  CAS  Google Scholar 

  64. Singh N, Manshian B, Jenkins GJ, et al. NanoGenotoxicology: the DNA damaging potential of engineered nanomaterials. Biomaterials. Epub 2009 May 6

  65. Choi AO, Brown SE, Szyf M, et al. Quantum dot-induced epigenetic and genotoxic changes in human breast cancer cells. J Mol Med 2008; 86(3): 291–302

    Article  PubMed  CAS  Google Scholar 

  66. Baccarelli A, Wright RO, Bollati V, et al. Rapid DNA methylation changes after exposure to traffic particles. Am J Respir Crit Care Med 2009; 179(7): 572–8

    Article  PubMed  CAS  Google Scholar 

  67. Donaldson K, Stone V. Current hypotheses on the mechanisms of toxicity of ultrafine particles. Ann Ist Super Sanita 2003; 39(3): 405–10

    PubMed  CAS  Google Scholar 

  68. Nel A, Xia T, Madler L, et al. Toxic potential of materials at the nanolevel. Science 2006; 311(5761): 622–7

    Article  PubMed  CAS  Google Scholar 

  69. Poland CA, Duffin R, Kinloch I, et al. Carbon nanotubes introduced into the abdominal cavity of mice show asbestos-like pathogenicity in a pilot study. Nat Nano 2008; 3(7): 423–8

    Article  CAS  Google Scholar 

  70. Muller J, Decordier I, Hoet PH, et al. Clastogenic and aneugenic effects of multi-wall carbon nanotubes in epithelial cells. Carcinogenesis 2008; 29(2): 427–33

    Article  PubMed  CAS  Google Scholar 

  71. Semmler-Behnke M, Kreyling WG, Lipka J, et al. Biodistribution of 1.4- and 18-nm gold particles in rats. Small 2008; 4(12): 2108–11

    Article  PubMed  CAS  Google Scholar 

  72. Takenaka S, Karg E, Kreyling WG, et al. Distribution pattern of inhaled ultrafine gold particles in the rat lung. Inhal Toxicol 2006; 18(10): 733–40

    Article  PubMed  CAS  Google Scholar 

  73. Dumortier H, Lacotte S, Pastorin G, et al. Functionalized carbon nanotubes are non-cytotoxic and preserve the functionality of primary immune cells. Nano Lett 2006; 6(7): 1522–8

    Article  PubMed  CAS  Google Scholar 

  74. Monteiller C, Tran L, MacNee W, et al. The proinflammatory effects of low-toxicity low-solubility particles, nanoparticles and fine particles, on epithelial cells in vitro: the role of surface area. Occup Environ Med 2007; 64(9): 609–15

    Article  PubMed  CAS  Google Scholar 

  75. Singh S, Shi T, Duffin R, et al. Endocytosis, oxidative stress and IL-8 expression in human lung epithelial cells upon treatment with fine and ultrafine TiO2: role of the specific surface area and of surface methylation of the particles. Toxicol Appl Pharmacol 2007; 222(2): 141–51

    Article  PubMed  CAS  Google Scholar 

  76. Gheshlaghi ZN, Riazi GH, Ahmadian S, et al. Toxicity and interaction of titanium dioxide nanoparticles with microtubule protein. Acta Biochim Biophys Sin (Shanghai) 2008; 40: 777–82

    CAS  Google Scholar 

  77. Lipski AM, Pino CJ, Haselton FR, et al. The effect of silica nanoparticle-modified surfaces on cell morphology, cytoskeletal organization and function. Biomaterials 2008; 29: 3836–46

    Article  PubMed  CAS  Google Scholar 

  78. Kaiser JP, Wick P, Manser P, et al. Single walled carbon nanotubes (SWCNT) affect cell physiology and cell architecture. J Mater Sci Mater Med 2008; 19: 1523–7

    Article  PubMed  CAS  Google Scholar 

  79. Putman E, van der Laan JW, van LH. Assessing immunotoxicity: guidelines. Fundam Clin Pharmacol 2003; 17(5): 615–26

    Article  PubMed  CAS  Google Scholar 

  80. Putman E, van der Laan JW, van Loveren H. Assessing immunotoxicity: guidelines. Fundam Clin Pharmacol 2003; 17: 615–26

    Article  PubMed  CAS  Google Scholar 

  81. Izhaky D, Pecht I. What else can the immune system recognize? ProcNatl Acad Sci U S A 1998; 95(20): 11509–10

    Article  CAS  Google Scholar 

  82. Mitchell LA, Gao J, Wal RV, et al. Pulmonary and systemic immune response to inhaled multiwalled carbon nanotubes. Toxicol Sci 2007; 100(1): 203–14

    Article  PubMed  CAS  Google Scholar 

  83. Nygaard UC, Samuelsen M, Aase A, et al. The capacity of particles to increase allergic sensitization is predicted by particle number and surface area, not by particle mass. Toxicol Sci 2004; 82: 515–24

    Article  PubMed  CAS  Google Scholar 

  84. Don Porto CA, Hoet PH, Verschaeve L, et al. Genotoxic effects of carbon black particles, diesel exhaust particles, and urban air particulates and their extracts on a human alveolar epithelial cell line (A549) and a human monocytic cell line (THP-1). Environ Mol Mutagen 2001; 37: 155–63

    Article  Google Scholar 

  85. Don Porto CA, Hoet PH, Nemery B, et al. HLA-DR expression after exposure of human monocytic cells to air particulates. Clin Exp Allergy 2002; 32(2): 296–300

    Article  Google Scholar 

  86. Van ZM, Granum B. Adjuvant activity of particulate pollutants in different mouse models. Toxicology 2000; 152(1–3): 69–77

    Google Scholar 

  87. Goodman CM, McCusker CD, Yilmaz T, et al. Toxicity of gold nanoparticles functionalized with cationic and anionic side chains. Bioconjug Chem 2004; 15(4): 897–900

    Article  PubMed  CAS  Google Scholar 

  88. Bottini M, Bruckner S, Nika K, et al. Multi-walled carbon nanotubes induce T lymphocyte apoptosis. Toxicol Lett 2006; 160(2): 121–6

    Article  PubMed  CAS  Google Scholar 

  89. Fiorito S, Serafino A, Andreola F, et al. Toxicity and biocompatibility of carbon nanoparticles. J Nanosci Nanotechnol 2006; 6(3): 591–9

    Article  PubMed  CAS  Google Scholar 

  90. Chen YW, Hwang KC, Yen CC, et al. Fullerene derivatives protect against oxidative stress in RAW 264.7 cells and ischemia-reperfused lungs. Am J Physiol Regul Integr Comp Physiol 2004; 287(1): R21–6

    Article  PubMed  CAS  Google Scholar 

  91. Barlow PG, Brown DM, Donaldson K, et al. Reduced alveolar macrophage migration induced by acute ambient particle (PM(10)) exposure. Cell Biol Toxicol 2008; 24(3): 243–52

    Article  PubMed  CAS  Google Scholar 

  92. Brown DM, Kinloch IA, Bangert U, et al. An in vitro study of the potential of carbon nanotubes and nanofibres to induce inflammatory mediators and frustrated phagocytosis. Carbon 2007; 45(9): 1743–56

    Article  CAS  Google Scholar 

  93. Shaunak S, Thomas S, Gianasi E, et al. Polyvalent dendrimer glucosamine conjugates prevent scar tissue formation. Nat Biotechnol 2004; 22(8): 977–84

    Article  PubMed  CAS  Google Scholar 

  94. Cromer JR, Wood SJ, Miller KA, et al. Functionalized dendrimers as endotoxin sponges. Bioorg Med Chem Lett 2005; 15(5): 1295–8

    Article  PubMed  CAS  Google Scholar 

  95. Shvedova AA, Fabisiak JP, Kisin ER, et al. Sequential exposure to carbon nanotubes and bacteria enhances pulmonary inflammation and infectivity. Am J Respir Cell Mol Biol 2008; 38(5): 579–90

    Article  PubMed  CAS  Google Scholar 

  96. Hoek G, Brunekreef B, Fischer P, et al. The association between air pollution and heart failure, arrhythmia, embolism, thrombosis, and other cardiovascular causes of death in a time series study. Epidemiology 2001; 12(3): 355–7

    Article  PubMed  CAS  Google Scholar 

  97. Pope III CA, Verrier RL, Lovett EG, et al. Heart rate variability associated with particulate air pollution. Am Heart J 1999; 138 (5 Pt 1): 890–9

    Article  PubMed  Google Scholar 

  98. Samet JM, Dominici F, Curriero FC, et al. Fine particulate air pollution and mortality in 20 US cities, 1987–1994. N Engl J Med 2000; 343(24): 1742–9

    Article  PubMed  CAS  Google Scholar 

  99. Baccarelli A, Zanobetti A, Martinelli I, et al. Effects of exposure to air pollution on blood coagulation. J Thromb Haemost 2007; 5(2): 252–60

    Article  PubMed  CAS  Google Scholar 

  100. Nemmar A, Hoylaerts MF, Hoet PH, et al. Size effect of intratracheally instilled particles on pulmonary inflammation and vascular thrombosis. Toxicol Appl Pharmacol 2003; 186(1): 38–45

    Article  PubMed  CAS  Google Scholar 

  101. Niwa Y, Iwai N. Nanomaterials induce oxidized low-density lipoprotein cellular uptake in macrophages and platelet aggregation. Circ J 2007; 71(3): 437–44

    Article  PubMed  CAS  Google Scholar 

  102. Russell JC, Proctor SD. Small animal models of cardiovascular disease: tools for the study of the roles of metabolic syndrome, dyslipidemia, and atherosclerosis. Cardiovasc Pathol 2006; 15(6): 318–30

    Article  PubMed  CAS  Google Scholar 

  103. Tran CL, Buchanan D, Cullen RT, et al. Inhalation of poorly soluble particles: II. Influence of particle surface area on inflammation and clearance. Inhal Toxicol 2000; 12(12): 1113–26

    Article  PubMed  CAS  Google Scholar 

  104. EMEA. Reflection paper on nanotechnology-based medicinal products for human use, 29 June 2006 [online]. Available from URL: http://www.emea.europa.eu/pdfs/human/genetherapy/7976906en.pdf [Accessed 2009 May 29]

  105. D’Silva J, Van Calster G. Taking temperature: a review of European Union regulation in nanomedicine (October 15, 2008) [online]. Available from URL: http://ssrn.com/abstract=1285099 [Accessed 2009 Jun 03]

  106. EMEA. Mandate of the EMEA Innovation Task Force (ITF), 11 April 2006 [online]. Available from URL: http://www.emea.europa.eu/pdfs/human/itf/itfmandate.pdf [Accessed 2009 May 29]

  107. FDA. Nanotechnology: a report of the US Food and Drug Administration Nanotechnology Task Force, 25 July 2007 [online]. Available from URL: http://www.fda.gov/nanotechnology/taskforce/report2007.html

  108. Alderson NE. Is special FDA regulation of nanomedicine needed? A conversation with Norris E. Alderson — interview by Barbara J. Culliton. Health Aff (Millwood) 2008; 27(4): w315–7

    Article  Google Scholar 

  109. Gaspar R. Regulatory issues surrounding nanomedicines: setting the scene for the next generation of nanopharmaceuticals. Nanomedicine 2007; 2: 143–7

    Article  PubMed  CAS  Google Scholar 

  110. Resnik DB, Tinkle SS. Ethical issues in clinical trials involving nanomedicine. Contemp Clin Trials 2007; 28: 433–41

    Article  PubMed  Google Scholar 

  111. DeVille KA. Law, regulation and the medical use of nanotechnology. In: Jotterand F, editor. Emerging conceptual, ethical and policy issues in bionanotechnology. Philosophy and medicine. Vol. 101. Dordrecht: Springer, 2008: 181–200

    Chapter  Google Scholar 

Download references

Acknowledgements

This reveiw had the financial support of the European Commission through the Sixth Framework Programmes for research and technological development NMP2-CT-2005-515843 contract ‘NANOSAFE2’ and SAS6-CT-2006-036754 contract ‘NANOCAP’. The authors have no conflicts of interest that are directly relevant to the content of this review.

Author information

Authors and Affiliations

  1. K.U. Leuven, Faculty of Medicine, Department of Public Health Occupational, Environmental & Insurance Medicine, Laboratorium voor Pneumologie (Longtoxicologie), Herestraat 49 (O&N1 unit 706), B-3000, Leuven, Belgium

    Peter Hoet, Barbara Legiest, Jorina Geys & Benoit Nemery

  2. Department of Pathophysiology and Pneumology, Laboratorium voor Pneumologie (Longtoxicologie), Leuven, Belgium

    Peter Hoet, Barbara Legiest, Jorina Geys & Benoit Nemery

Authors
  1. Peter Hoet
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Barbara Legiest
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jorina Geys
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Benoit Nemery
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter Hoet.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hoet, P., Legiest, B., Geys, J. et al. Do Nanomedicines Require Novel Safety Assessments to Ensure their Safety for Long-Term Human Use?. Drug-Safety 32, 625–636 (2009). https://doi.org/10.2165/00002018-200932080-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002018-200932080-00002

Keywords

Search

Navigation