Skip to main content
Log in

Comparison of the toxicity of aluminum oxide nanorods with different aspect ratio

  • Nanotoxicology
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

Aluminum oxide nanoparticles are listed among 14 high-priority nanomaterials published by the Organization for Economic Co-operation and Development, but limited information is available on their potential hazards. In this study, we compared the toxicity of two different aluminum oxide nanorods (AlNRs) commercially available in vivo and in vitro. Considering aspect ratio, one was 6.2 ± 0.6 (long-AlNRs) and the other was 2.1 ± 0.4 (short-AlNRs). In mice, long-AlNRs induced longer and stronger inflammatory responses than short-AlNRs, and the degree reached the maximum on day 7 for both types and decreased with time. In addition, in vitro tests were performed on six cell lines derived from potential target organs for AlNPs, HEK-293 (kidney), HACAT (skin), Chang (liver), BEAS-2B (lung), T98G (brain), and H9C2 (heart), using MTT assay, ATP assay, LDH release, and xCELLigence system. Long-AlNRs generally produced stronger toxicity than short-AlNRs, and HEK-293 cells were the most sensitive for both AlNRs, followed by BEAS-2B cells, although results from 4 kinds of toxicity tests conflicted among the cell lines. Based on these results, we suggest that toxicity of AlNRs may be related to aspect ratio (and resultant surface area). Furthermore, novel in vitro toxicity testing methods are needed to resolve questionable results caused by the unique properties of nanoparticles.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  • Almeida JP, Chen AL, Foster A, Drezek R (2011) In vivo biodistribution of nanoparticles. Nanomedicine (Lond) 6(5):815–835

    Article  CAS  Google Scholar 

  • Asati A, Santra S, Kaittanis C, Perez JM (2010) Surface-charge-dependent cell localization and cytotoxicity of cerium oxide nanoparticles. ACS Nano 4(9):5321–5331

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Cavaillon JM (1993) Contribution of cytokines to inflammatory mechanisms. Pathol Biol (Paris) 41(8Pt2): 799–811

  • DeBrosse MC, Comfort KK, Untener EA, Comfort DA, Hussain SM (2013) High aspect ratio gold nanorods displayed augmented cellular internalization and surface chemistry mediated cytotoxicity. Mater Sci Eng C Mater Biol Appl 33(7):4094–4100

    Article  CAS  PubMed  Google Scholar 

  • Di Gioacchino M, Petrarca C, Lazzarin F, Di Giampaolo L, Sabbioni E, Boscolo P, Mariani-Costantini R, Bernardini G (2011) Immunotoxicity of nanoparticles. Int J Immunopathol Pharmacol 24(1 Suppl):65S–71S

    PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Feliu N, Fadeel B (2010) Nanotoxicology: no small matter. Nanoscale 2:2514–2520

    Article  CAS  PubMed  Google Scholar 

  • Inoue K, Koike E, Yanaqisawa R, Hirano S, Nishikawa M, Takano H (2009) Effects of multi-walled carbon nanotubes on a murine allergic airway inflammation model. Toxicol Appl Pharmacol 237(3):306–316

    Article  CAS  PubMed  Google Scholar 

  • 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(2):370–377

    Article  CAS  PubMed  Google Scholar 

  • Kroll A, Pillukat MH, Hahn D, Schnekenburger J (2012) Interference of engineered nanoparticles with in vitro toxicity assays. Arch Toxicol 86(7):1123–1136

    Article  CAS  PubMed  Google Scholar 

  • Kumar V, Gill KD (2009) Aluminium neurotoxicity: neurobehavioural and oxidative aspects. Arch Toxicol 83(11):965–978

    Article  CAS  PubMed  Google Scholar 

  • Lanone S, Rogerieux F, Geys J, Dupont A, Maillot-Marechal E, Boczkowski J, Lacroix G, Hoet P (2009) Comparative toxicity of 24 manufactured nanoparticles in human alveolar epithelial and macrophage cell lines. Part Fibre Toxicol 6:14

    Article  PubMed Central  PubMed  Google Scholar 

  • Lin S, Wang X, Ji Z, Chang CH, Dong Y, Meng H, Liao YP, Wang M, Song TB, Kohan S, Xia T, Zink JI, Lin S, Nel AE (2014) Aspect ratio plays a role in the hazard potential of CeO2 nanoparticles in mouse lung and zebrafish gastrointestinal tract. ACS Nano 8(5):4450–4464

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ling D, Hyeon T (2013) Chemical design o f biocompatible iron oxide nanoparticles for medical applications. Small 9(9–10):1450–1466

    Article  CAS  PubMed  Google Scholar 

  • Lu S, Duffin R, Poland C, Daly P, Murphy F, Drost E, Macnee W, Stone V, Donaldson K (2009) Efficacy of simple short-term in vitro assays for predicting the potential of metal oxide nanoparticles to cause pulmonary inflammation. Environ Health Perspect 117(2):241–247

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Marques MRC, Loebenberg R, Almukainzi M (2011) Simulated biological fluids with possible application in dissolution testing. Dissolut Technol 8:15–28

    Article  Google Scholar 

  • Miu AC, Benga O (2006) Aluminium and Alzheimer’s disease: a new look. J Alzheimers Dis 10(2–3):179–201

    CAS  PubMed  Google Scholar 

  • 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(2):222–235

    Article  CAS  PubMed  Google Scholar 

  • Nel A, Xia T, Mädler L, Li N (2006) Toxic potential of materials at the nanolevel. Science 311:622–627

    Article  CAS  PubMed  Google Scholar 

  • Nel AE, Mädler L, Velegol D, Xia T, Heok EM, Somasundaran P, Klaessig F, Castranova V, Thompson M (2009) Understanding biophysicochemical interactions at the nano-bio interface. Nat Mater 8(7):543–557

    Article  CAS  PubMed  Google Scholar 

  • Nygaard UC, Hansen JS, Samuelsen M, Alberg T, Marioara CD, Løvik M (2009) Single-walled and multi-walled carbon nanotubes promote allergic immune responses in mice. Toxicol Sci 109(1):113–123

    Article  CAS  PubMed  Google Scholar 

  • Oberdörster G, Maynard A, Donaldson K, Castranova V, Fitzpatrick J, Ausman K, Carter J, Karn B, Kreyling W, Lai D, Olin S, Monteiro-Riviere N, Warheit D, Yang H, A report from the ILSI research foundation, risk science institute nanomaterials toxicity screening working group (2005) Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy. Part Fibre Toxicol 2:8

    Article  PubMed Central  PubMed  Google Scholar 

  • Oesterling E, Chopra N, Gavalas V, Arzuaga X, Lim EJ, Sultana R, Butterfield DA, Bachas L, Hennig B (2008) Alumina nanoparticles induce expression of endothelial cell adhesion molecules. Toxicol Lett 178(3):160–166

    Article  CAS  PubMed  Google Scholar 

  • Oyanagi K (2005) The nature of the parkinsonism-dementia complex and amyotrophic lateral sclerosis of Guam and magnesium deficiency. Parkinsonism Relat Disord 11(Suppl 1):S17–S23

    Article  PubMed  Google Scholar 

  • 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(3):113–121

    Article  CAS  PubMed  Google Scholar 

  • Park EJ, Kim H, Kim Y, Yi J, Choi K, Park K (2010) Inflammatory responses may be induced by a single intratracheal instillation of iron nanoparticles in mice. Toxicology 275(1–3):65–71

    Article  CAS  PubMed  Google Scholar 

  • Park EJ, Kim H, Kim Y, Choi K (2011) Repeated-dose toxicity attributed to aluminum nanoparticles following 28-day oral administration, particularly on gene expression in mouse brain. Toxicol Environ Chem 93(1):120–133

    Article  CAS  Google Scholar 

  • Park EJ, Shim JH, Kim Y, Han BS, Yoon C, Lee S, Cho MH, Lee BS, Kim JH (2014) A 13-weeks repeated dose oral toxicity and bioaccumulation of aluminum oxide nanoparticles in mice. Arch Toxicol Epub ahead of print

  • Park EJ, Umh HN, Kim SW, Cho MH, Kim JH, Kim Y (2014b) ERK pathway is activated in bare-FeNPs-induced autophagy. Arch Toxicol 88(2):323–336

    Article  CAS  PubMed  Google Scholar 

  • Pauluhn J (2009) Pulmonary toxicity and fate of agglomerated 10 and 40 nm aluminum oxyhydroxides following 4-week inhalation exposure of rats: toxic effects are determined by agglomerated, not primary particle size. Toxicol Sci 109(1):152–167

    Article  CAS  PubMed  Google Scholar 

  • Project on Emerging Nanotechnologies (Woodrow Wilson International Center) (2007) nanotech-safety-needs-specific-government-risk-research-strategy-and-funding, Jan 04

  • Rawat K, Agarwal S, Tyagi A, Verma AK, Bohidar HB (2014) Aspect ratio dependent cytotoxicity and anitmicrobial properties of nanoclay. Appl Biochem Biotechnol Epub ahead of print

  • Repetto G, del Peso A, Zurita JL (2008) Neutral red uptake assay for the estimation of cell viability/cytotoxicity. Nat Protoc 3(7):1125–1131

    Article  CAS  PubMed  Google Scholar 

  • Savory J, Herman MM, Ghribi O (2006) Mechanisms of aluminum-induced neurodegeneration in animals: implications for Alzheimer’s disease. J Alzheimers Dis 10(2–3):135–144

    PubMed  Google Scholar 

  • Souza Santosa P, Souza Santos H, Toledo SP (2000) Standard transition aluminas, electron microscopy studies. Mater Res 3(4):104–114

    Google Scholar 

  • Teow Y, Asharani PV, Hande MP, Valiyaveettil S (2011) Health impact and safety of engineered nanomaterials. Chem Commun 47:7025–7038

    Article  CAS  Google Scholar 

  • The national academy of sciences (2007) Toxicity testing in the 21st century: a vision and a strategy. http://nationalacacemies.org/best

  • Verma A, Stellacci F (2010) Effect of surface properties on nanoparticle-cell interactions. Small 6(1):12–21

    Article  CAS  PubMed  Google Scholar 

  • Vieira coelho AC, Rocha GA, Souza santos P, Souza Santos H, Kiyohara PK (2008) Specific surface area and structures of aluminas from fibrillar pseudoboehmite. Revista Matér 13(2):329–341

    Article  Google Scholar 

  • Wu Z, Du Y, Xue H, Wu Y, Zhou B (2012) Aluminum induces neurodegeneration and its toxicity arises from increased iron accumulation and reactive oxygen species (ROS) production. Neurobiol Aging 33(1):199.e1–199.e12

    Article  CAS  Google Scholar 

  • 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(6):683–690

    Article  PubMed Central  PubMed  Google Scholar 

  • Xu L, Zhang QL, Gao FP, Nie JS, Niu Q (2010) Cell toxicity assessment methodologies applied in the study of the toxicity of nano-alumina to nerve cells. Zhonghua Yu Fang Yi Xue Za Zhi 44(9):785–789

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (NRF-2011-35B-E00011). And, this research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and future Planning (2012R1A2A2A01045382).

Conflict of interest

The authors report no declarations of interest.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Eun-Jung Park or Dong-Wan Kim.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PPT 425 kb)

Supplementary material 2 (DOCX 22 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Park, EJ., Lee, GH., Shim, Jh. et al. Comparison of the toxicity of aluminum oxide nanorods with different aspect ratio. Arch Toxicol 89, 1771–1782 (2015). https://doi.org/10.1007/s00204-014-1332-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00204-014-1332-5

Keywords

Navigation