Journal of Molecular Medicine

, Volume 83, Issue 5, pp 377–385 | Cite as

Differences in subcellular distribution and toxicity of green and red emitting CdTe quantum dots

  • Jasmina Lovrić
  • Hassan S. Bazzi
  • Yan Cuie
  • Genevieve R. A. Fortin
  • Françoise M. Winnik
  • Dusica Maysinger
Original Article

Abstract

Quantum dots (QDs) are emerging as alternative or complementary tools to the organic fluorescent dyes currently used in bioimaging. QDs hold several advantages over conventional fluorescent dyes including greater photostability and a wider range of excitation/emission wavelengths. However, recent work suggests that QDs exert deleterious effects on cellular processes. This study examined the subcellular localization and toxicity of cadmium telluride (CdTe) QDs and pharmacological means of preventing QD-induced cell death. The localization of CdTe QDs was found to depend upon QD size. CdTe QDs exhibited marked cytotoxicity in PC12 and N9 cells at concentrations as low as 10 µg/ml in chronic treatment paradigms. QD-induced cell death was characterized by chromatin condensation and membrane blebbing and was more pronounced with small (2r=2.2±0.1 nm), green emitting positively charged QDs than large (2r=5.2±0.1 nm), equally charged red emitting QDs. Pretreatment of cells with the antioxidant N-acetylcysteine and with bovine serum albumin, but not Trolox, significantly reduced the QD-induced cell death. These findings suggest that the size of QDs contributes to their subcellular distribution and that drugs can alter QD-induced cytotoxicity.

Keywords

Quantum dots Fluorescence Toxicity Cell death Antioxidants 

Abbreviations

BSA

Bovine serum albumin

CdSe

Cadmium selenide

CdTe

Cadmium telluride

DAF

5-Dodecanoylaminofluorescein

MPA

Mercaptopropionic acid

MTT

3-(4,5-Dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide

NAC

N-Acetylcysteine

PBS

Phosphate-buffered saline

QD

Quantum dot

Notes

Acknowledgements

This work was supported by the Juvenile Diabetes Research Foundation (Canada) and NanoQuebec. We thank Dr. E. Kumacheva (Department of Chemistry, University of Toronto) for helpful discussions and for suggestions on the preparation of water soluble QDs. J.L. also thanks J. Tam and R. Aikin for useful discussion and stylistic revisions of the manuscript.

References

  1. 1.
    Chan WC, Nie S (1998) Quantum dot bioconjugates for ultrasensitive nonisotopic detection. Science 281:2016–2018CrossRefPubMedGoogle Scholar
  2. 2.
    Chan WC, Maxwell DJ, Gao X, Bailey RE, Han M, Nie S (2002) Luminescent quantum dots for multiplexed biological detection and imaging. Curr Opin Biotechnol 13:40–46CrossRefGoogle Scholar
  3. 3.
    Jovin TM (2003) Quantum dots finally come of age. Nat Biotechnol 21:32–33CrossRefPubMedGoogle Scholar
  4. 4.
    Mattoussi H, Mauro JM, Goldman ER, Anderson GP, Sundar VC, Mikulec FV, Bawendi MG (2000) Self-assembly of CdSe-ZnS quantum dot bioconjugates using an engineered recombinant protein. J Am Chem Soc 122:12142–12150CrossRefGoogle Scholar
  5. 5.
    Dabbousi BO, Rodriguez-Viejo J, Mikulec FV, Heine JR, Mattoussi H, Ober R, Jensen KF, Bawendu MG (1997) (CdSe) ZnS core shell quantum dots: synthesis and characterization of a size series of highly luminescent nanocrystallites. J Phys Chem B 101:9463–9475CrossRefGoogle Scholar
  6. 6.
    Pathak S, Choi SK, Arnheim N, Thompson ME (2001) Hydroxylated quantum dots as luminescent probes for in situ hybridization. J Am Chem Soc 123:4103–4104CrossRefPubMedGoogle Scholar
  7. 7.
    Wuister SF, Swart I, van Driel F, Hickey SG, Donega CD (2003) Highly luminescent water-soluble CdTe quantum dots. Nano Lett 3:503–507CrossRefGoogle Scholar
  8. 8.
    Gao M, Kirstein S, Mvhwald H, Rogach AL, Kornovski A, Eyhmiller A, Weller Horst (1998) Strongly photoluminescent CdTe nanocrystals by proper surface modification. J Phys Chem B 102:8360–8363CrossRefGoogle Scholar
  9. 9.
    Lidke DS, Nagy P, Heintzmann R, rndt-Jovin DJ, Post JN, Grecco HE, Jares-Erijman EA, Jovin TM (2004) Quantum dot ligands provide new insights into erbB/HER receptor-mediated signal transduction. Nat Biotechnol 22:198–203CrossRefGoogle Scholar
  10. 10.
    Dahan M, Levi S, Luccardini C, Rostaing P, Riveau B, Triller A (2003) Diffusion dynamics of glycine receptors revealed by single-quantum dot tracking. Science 302:442–445CrossRefGoogle Scholar
  11. 11.
    Dubertret B, Skourides P, Norris DJ, Noireaux V, Brivanlou AH, Libchaber A (2002) In vivo imaging of quantum dots encapsulated in phospholipid micelles. Science 298:1759–1762CrossRefPubMedGoogle Scholar
  12. 12.
    Gao X, Nie S (2003) Molecular profiling of single cells and tissue specimens with quantum dots. Trends Biotechnol 21:371–373CrossRefGoogle Scholar
  13. 13.
    Bruchez M Jr, Moronne M, Gin P, Weiss S, Alivisatos AP (1998) Semiconductor nanocrystals as fluorescent biological labels. Science 281:2013–2016CrossRefPubMedGoogle Scholar
  14. 14.
    Parak WJ, Boudreau R, Le Gros M, Gerion D, Zanchet D, Micheel CM, Williams SC, Alivisatos AP, Larabell C (2002) Cell motility and metastatic potential studies based on quantum dot imaging of phagokinetic tracks. Adv Mater 14:882–885CrossRefGoogle Scholar
  15. 15.
    Jaiswal JK, Mattoussi H, Mauro JM, Simon SM (2003) Long-term multiple color imaging of live cells using quantum dot bioconjugates. Nat Biotechnol 21:47–51CrossRefGoogle Scholar
  16. 16.
    Wu X, Liu H, Liu J, Haley KN, Treadway JA, Larson JP, Ge N, Peale F, Bruchez MP (2003) Immunofluorescent labeling of cancer marker Her2 and other cellular targets with semiconductor quantum dots. Nat Biotechnol 21:41–46CrossRefPubMedGoogle Scholar
  17. 17.
    Derfus AM, Chan WCW, Bhatia SN (2004) Probing the cytotoxicity of semiconductor quantum dots. Nano Lett 4:11–18CrossRefGoogle Scholar
  18. 18.
    Magde D, Wong R, Seybold PG (2002) Fluorescence quantum yields and their relation to lifetimes of rhodamine 6G and fluorescein in nine solvents: improved absolute standards for quantum yields. Photochem Photobiol 75:327–334CrossRefGoogle Scholar
  19. 19.
    Hermanson GT (1996) Bioconjugate techniques. Academic Press, New YorkGoogle Scholar
  20. 20.
    Mamedova NN, Kotov NA, Rogach AL, Studer J (2001) Albumin-CdTe nanoparticle bioconjugates: preparation, structure, and interunit energy transfer with antenna effect. Nano Lett 1:281–286CrossRefGoogle Scholar
  21. 21.
    Poliandri AH, Cabilla JP, Velardez MO, Bodo CC, Duvilanski BH (2003) Cadmium induces apoptosis in anterior pituitary cells that can be reversed by treatment with antioxidants. Toxicol Appl Pharmacol 190:17–24CrossRefGoogle Scholar
  22. 22.
    Almazan G, Liu HN, Khorchid A, Sundararajan S, Martinez-Bermudez AK, Chemtob S (2000) Exposure of developing oligodendrocytes to cadmium causes HSP72 induction, free radical generation, reduction in glutathione levels, and cell death. Free Radic Biol Med 29:858–869CrossRefPubMedGoogle Scholar
  23. 23.
    Warren S, Patel S, Kapron CM (2000) The effect of vitamin E exposure on cadmium toxicity in mouse embryo cells in vitro. Toxicology 142:119–126CrossRefGoogle Scholar
  24. 24.
    Weis K (2003) Regulating access to the genome: nucleocytoplasmic transport throughout the cell cycle. Cell 112:441–451CrossRefGoogle Scholar
  25. 25.
    Shiohara A, Hoshino A, Hanaki K, Suzuki K, Yamamoto K (2004) On the cyto-toxicity caused by quantum dots. Microbiol Immunol 48:669–675Google Scholar
  26. 26.
    Sies H, Murphy ME (1991) Role of tocopherols in the protection of biological systems against oxidative damage. J Photochem Photobiol B 8:211–218CrossRefGoogle Scholar
  27. 27.
    Bisby RH, Parker AW (1995) Reaction of ascorbate with the alpha-tocopheroxyl radical in micellar and bilayer membrane systems. Arch Biochem Biophys 317:170–178CrossRefGoogle Scholar
  28. 28.
    Cotgreave IA (1997) N-Acetylcysteine: pharmacological considerations and experimental and clinical applications. Adv Pharmacol 38:205–227Google Scholar
  29. 29.
    Yan CY, Ferrari G, Greene LA (1995) N-Acetylcysteine-promoted survival of PC12 cells is glutathione-independent but transcription-dependent. J Biol Chem 270:26827–26832CrossRefGoogle Scholar
  30. 30.
    Yan CY, Greene LA (1998) Prevention of PC12 cell death by N-acetylcysteine requires activation of the Ras pathway. J Neurosci 18:4042–4049Google Scholar
  31. 31.
    Moosmann B, Behl C (2002) Secretory peptide hormones are biochemical antioxidants: structure-activity relationship. Mol Pharmacol 61:260–268CrossRefGoogle Scholar
  32. 32.
    Hanaki K, Momo A, Oku T, Komoto A, Maenosono S, Yamaguchi Y, Yamamoto K (2003) Semiconductor quantum dot/albumin complex is a long-life and highly photostable endosome marker. Biochem Biophys Res Commun 302:496–501CrossRefGoogle Scholar
  33. 33.
    Belyaeva EA, Korotkov SM (2003) Mechanism of primary Cd2+-induced rat liver mitochondria dysfunction: discrete modes of Cd2+ action on calcium and thiol-dependent domains. Toxicol Appl Pharmacol 192:56–68CrossRefGoogle Scholar
  34. 34.
    Wispriyono B, Matsuoka M, Igisu H, Matsuno K (1998) Protection from cadmium cytotoxicity by N-acetylcysteine in LLC-PK1 cells. J Pharmacol Exp Ther 287:344–351Google Scholar
  35. 35.
    Sadler PJ, Viles JH (1996) H-1 and Cd-113 NMR investigations of Cd2+ and Zn2+ binding sites on serum albumin: competition with Ca2+, Ni2+, Cu2+, and Zn2+. Inorg Chem 35:4490–4496CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Jasmina Lovrić
    • 1
  • Hassan S. Bazzi
    • 2
  • Yan Cuie
    • 2
  • Genevieve R. A. Fortin
    • 1
  • Françoise M. Winnik
    • 2
  • Dusica Maysinger
    • 1
  1. 1.Department of Pharmacology and TherapeuticsMcGill UniversityMontrealCanada
  2. 2.Faculty of Pharmacy and Department of ChemistryUniversite de MontrealMontrealCanada

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