Quantum Dots and Other Fluorescent Nanoparticles: Quo Vadis in the Cell?

  • Dusica Maysinger
  • Jasmina Lovrić
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 620)


An exponentially growing number of nanotechnology-based products are providing new platforms for research in different scientific disciplines (e.g., life sciences and medicine). Biocompatible nanoparticles are expected to significantly impact the development of new approaches in medical diagnoses and drug delivery; however, very little is known about the effects of long-term exposure of different nanoparticles in different cell types and tissues. The first objective of this chapter is to provide a brief account of the current status of fluorescent nanoparticles (i.e., quantum dots, fluorescently-labeled micelles, and FloDots) that serve as tools for bioimaging and therapeutics. The second objective of this chapter is to describe the modes and mechanisms of nanoparticle-cell interactions and the “potential” toxic consequences thereof.


Endoplasmic Reticulum Stress Unfold Protein Response Polymeric Micelle Fluorescent Nanoparticles Block Copolymer Micelle 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Ferrari M. Cancer nanotechnology: Opportunities and challenges. Nat Rev Cancer 2005; 5(3):161–171.PubMedCrossRefGoogle Scholar
  2. 2.
    Silva GA. Neuroscience nanotechnology: Progress, opportunities and challenges. Nat Rev Neurosci 2006; 7(1):65–74.PubMedCrossRefGoogle Scholar
  3. 3.
    Bakalova R, Ohba H, Zhelev Z et al. Quantum dots as photosensitizers? Nat Biotechnol 2004; 22(11):1360–1361.PubMedCrossRefGoogle Scholar
  4. 4.
    Kam NW, O’Connell M, Wisdom JA et al. Carbon nanotubes as multifunctional biological transporters and near-infrared agents for selective cancer cell destruction. Proc Natl Acad Sci USA 2005; 102(33):11600–11605.PubMedCrossRefGoogle Scholar
  5. 5.
    Jain KK. Nanoparticles as targeting ligands. Trends Biotechnol 2006; 24(4):143–145.PubMedCrossRefGoogle Scholar
  6. 6.
    Weissleder R, Kelly K, Sun EY et al. Cell-specific targeting of nanoparticles by multivalent attachment of small molecules. Nat Biotechnol 2005; 23(11):1418–1423.PubMedCrossRefGoogle Scholar
  7. 7.
    Giepmans BN, Adams SR, Ellisman MH et al. The fluorescent toolbox for assessing protein location and function. Science 2006;312(5771):217–224.PubMedCrossRefGoogle Scholar
  8. 8.
    Medintz IL, Uyeda HT, Goldman ER et al. Quantum dot bioconjugates for imaging, labelling and sensing. Nat Mater 2005; 4(6):435–446.PubMedCrossRefGoogle Scholar
  9. 9.
    Jaiswal JK, Mattoussi H, Mauro JM et al. Long-term multiple color imaging of live cells using quantum dot bioconjugates. Nat Biotechnol 2003; 21(1):47–51.PubMedCrossRefGoogle Scholar
  10. 10.
    Yao G, Wang L, Wu Y et al. FloDots: Luminescent nanoparticles. Anal Bioanal Chem 2006; 385(3):518–524.PubMedCrossRefGoogle Scholar
  11. 11.
    Savic R, Eisenberg A, Maysinger D. Block copolymer micelles as delivery vehicles of hydrophobic drugs: Micelle-cell interactions. J Drug Target 2006; 14(6):343–355.PubMedCrossRefGoogle Scholar
  12. 12.
    Savic R, Luo L, Eisenberg A et al. Micellar nanocontainers distribute to defined cytoplasmic organelles. Science 2003; 300(5619):615–618.PubMedCrossRefGoogle Scholar
  13. 13.
    Alivisatos AP. Semiconductor Clusters, Nanocrystals, and Quantum Dots. Science 1996; 271:933–937.CrossRefGoogle Scholar
  14. 14.
    Dahan M, Levi S, Luccardini C et al. Diffusion dynamics of glycine receptors revealed by single-quantum dot tracking. Science 2003; 302(5644):442–445.PubMedCrossRefGoogle Scholar
  15. 15.
    Larson DR, Zipfel WR, Williams RM et al. Water-soluble quantum dots for multiphoton fluorescence imaging in vivo. Science 2003; 300(5624):1434–1436.PubMedCrossRefGoogle Scholar
  16. 16.
    Maysinger D, Berezovska O, Savic R et al. Block copolymers modify the internalization of micelle-incorporated probes into neural cells. Biochim Biophys Acta 2001; 1539(3):205–217.PubMedCrossRefGoogle Scholar
  17. 17.
    Torchilin VP. Fluorescence microscopy to follow the targeting of liposomes and micelles to cells and their intracellular fate. Adv Drug Deliv Rev 2005; 57(1):95–109.PubMedCrossRefGoogle Scholar
  18. 18.
    Allen C, Yu Y, Eisenberg A et al. Cellular internalization of PCL(20)-b-PEO(44) block copolymer micelles. Biochim Biophys Acta 1999;1421(1):32–38.PubMedCrossRefGoogle Scholar
  19. 19.
    Philipp Seib F, Jones AT, Duncan R. Establishment of subcellular fractionation techniques to monitor the intracellular fate of polymer therapeutics I: Differential centrifugation fractionation B16F10 cells and use to study the intracellular fate of HPMA copolymer-doxorubicin. J Drug Target 2006; 14(6):375–390.PubMedCrossRefGoogle Scholar
  20. 20.
    Duncan R. Polymer conjugates an anticancer nanomedicines. Nat Rev Cancer 2006; 6(9):688–701.PubMedCrossRefGoogle Scholar
  21. 21.
    Maeda H, Wu J, Sawa T et al. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: A review. J Control Release 2000; 65(1–2):271–284.PubMedCrossRefGoogle Scholar
  22. 22.
    Wang L, Yang C, Tan W. Dual-luminophore-doped silica nanoparticles for multiplexed signaling. Nano Lett 2005; 5(1):37–43.PubMedCrossRefGoogle Scholar
  23. 23.
    Pathak S, Cao E, Davidson MC et al. Quantum dot applications to neuroscience: New tools for probing neurons and glia. J Neurosci 2006; 26(7):1893–1895.PubMedCrossRefGoogle Scholar
  24. 24.
    Gaponik N, Talapin DV, Rogach AL et al. Thiol-capping of CdTe nanocrystals: An alternative to organometallic synthetic routes. J Phys Chem B 2002; 106:7177–7185.CrossRefGoogle Scholar
  25. 25.
    Chan WC, Nie S. Quantum dot bioconjugates for ultrasensitive nonisotopic detection. Science 1998; 281(5385):2016–2018.PubMedCrossRefGoogle Scholar
  26. 26.
    Pavlovic E, Quist AP, Gelius U et al. Surface functionalization of silicon oxide at room temperature and atmospheric pressure. J Colloid Interface Sci 2002; 54(1):200–203.CrossRefGoogle Scholar
  27. 27.
    Pinaud F, King D, Moore HP et al. Bioactivation and cell targeting of semiconductor CdSe/ZnS nanocrystals with phytochelatin-related peptides. J Am Chem Soc 2004; 126(19):6115–6123.PubMedCrossRefGoogle Scholar
  28. 28.
    Dubertret B, Skourides P, Norris DJ et al. In vivo imaging of quantum dots encapsulated in phospholipid micelles. Science 2002; 298(5599):1759–1762.PubMedCrossRefGoogle Scholar
  29. 29.
    Gao X, Cui Y, Levenson RM et al. In vivo cancer targeting and imaging with semiconductor quantum dots. Nat Biotechnol 2004; 22(8):969–976.PubMedCrossRefGoogle Scholar
  30. 30.
    Bharali DJ, Lucey DW, Jayakumar H et al. Folate-receptor-mediated delivery of InP quantum dots for bioimaging using confocal and two-photon microscopy. J Am Chem Soc 2005; 127(32):11364–11371.PubMedCrossRefGoogle Scholar
  31. 31.
    Wu X, Liu H, Liu J et al. Immunofluorescent labeling of cancer marker Her2 and other cellular targets with semiconductor quantum dots. Nat Biotechnol 2003; 21(1):41–46.PubMedCrossRefGoogle Scholar
  32. 32.
    Hoshino A, Fujioka K, Oku T et al. Quantum dots targeted to the assigned organelle in living cells. Microbiol Immunol 2004; 48(12):985–994.PubMedGoogle Scholar
  33. 33.
    Vu TQ, Maddipati R, Blute TA et al. Peptide-conjugated quantum dots activate neuronal receptors and initiate downstream signaling of neurite growth. Nano Lett 2005; 5(4):603–607.PubMedCrossRefGoogle Scholar
  34. 34.
    Hermanson GT. Bioconjugate Techniques. San Diego: Academic Press, 1996.Google Scholar
  35. 35.
    Torchilin VP, Narula J, Halpern E et al. Poly (ethylene glycol)-coated anti-cardiac myosin immunoliposomes: Factors influencing targeted accumulation in the infarcted myocardium. Biochim Biophys Acta 1996; 1279(1):75–83.PubMedCrossRefGoogle Scholar
  36. 36.
    Torchilin VP, Lukyanov AN, Gao Z et al. Immunomicelles: Targeted pharmaceutical carriers for poorly soluble drugs. Proc Natl Acad Sci USA 2003; 100(10):6039–6044.PubMedCrossRefGoogle Scholar
  37. 37.
    Savic R, Azzam T, Eisenberg A et al. Assessment of the integrity of poly(caprolactone)-b-poly(ethylene oxide) micelles under biological conditions: A fluorogenic-based approach. Langmuir 2006; 22(8):3570–3578.PubMedCrossRefGoogle Scholar
  38. 38.
    Michalet X, Pinaud FF, Bentolila LA et al. Quantum dots for live cells, in vivo imaging, and diagnostics. Science 2005; 307(5709):538–544.PubMedCrossRefGoogle Scholar
  39. 39.
    Jiang W, Papa E, Fischer H et al. Semiconductor quantum dots as contrast agents for whole animal imaging. Trends Biotechnol 2004; 22(12):607–609.PubMedCrossRefGoogle Scholar
  40. 40.
    Aldana J, Lavelle N, Wang Y et al. Size-dependent dissociation pH of thiolate ligands from cadmium chalcogenide nanocrystals. J Am Chem Soc 2005; 127(8):2496–2504.PubMedCrossRefGoogle Scholar
  41. 41.
    Aldana J, Wang YA, Peng X. Photochemical instability of CdSe nanocrystals coated by hydrophilic thiols. J Am Chem Soc 2001; 123(36):8844–8850.PubMedCrossRefGoogle Scholar
  42. 42.
    Rossin R, Pan D, Qi K et al. 64Cu-labeled folate-conjugated shell cross-linked nanoparticles for tumor imaging and radiotherapy: Synthesis, radiolabeling, and biologic evaluation. J Nucl Med 2005; 46(7):1210–1218.PubMedGoogle Scholar
  43. 43.
    Thurmond KB, Kowalewski T, Wooley KL. Shell cross-linked knedels: A synthetic study of the factors affecting the dimensions and properties of amphiphilic core-shell nanospheres. J Am Chem Soc 1997; 119(28):6656–6665.CrossRefGoogle Scholar
  44. 44.
    Thurmond KB, Kowalewski T, Wooley KL. Water-soluble knedel-like structures: The preparation of shell-cross-linked small particles. J Am Chem Soc 1996; 118(30):7239–7240.CrossRefGoogle Scholar
  45. 45.
    Cheng C, Qi K, Khoshdel E et al. Tandem synthesis of core-shell brush copolymers and their transformation to peripherally cross-linked and hollowed nanostructures. J Am Chem Soc 2006; 128(21):6808–6809.PubMedCrossRefGoogle Scholar
  46. 46.
    Joralemon MJ, O’Reilly RK, Hawker CJ et al. Shell click-crosslinked (SCC) nanoparticles: A new methodology for synthesis and orthogonal functionalization. J Am Chem Soc 2005; 127(48):16892–16899.PubMedCrossRefGoogle Scholar
  47. 47.
    Kim S, Lim YT, Soltesz EG et al. Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping. Nat Biotechnol 2004; 22(1):93–97.PubMedCrossRefGoogle Scholar
  48. 48.
    Voura EB, Jaiswal JK, Mattoussi H et al. Tracking metastatic tumor cell extravasation with quantum dot nanocrystals and fluorescence emission-scanning microscopy. Nat Med 2004; 10(9):993–998.PubMedCrossRefGoogle Scholar
  49. 49.
    So MK, Xu C, Loening AM et al. Self-illuminating quantum dot conjugates for in vivo imaging. Nat Biotechnol 2006; 24(3):339–343.PubMedCrossRefGoogle Scholar
  50. 50.
    Akerman ME, Chan WC, Laakkonen P et al. Nanocrystal targeting in vivo. Proc Natl Acad Sci USA 2002; 99(20):12617–12621.PubMedCrossRefGoogle Scholar
  51. 51.
    Fisher HC, Liu L, Pang SK et al. Pharmacokinetics of nanoscale quantum dots: In vivo distribution, Sequestration, and clearance in the rat. Adv Function Mater 2006; 16(10):1299–1305.CrossRefGoogle Scholar
  52. 52.
    Murphy L. Biosensors and bioelectrochemistry. Curr Opin Chem Biol 2006; 10(2):177–184.PubMedCrossRefGoogle Scholar
  53. 53.
    Zhang Y, Lim CT, Ramakrishna S et al. Recent development of polymer nanofibers for biomedical and biotechnological applications. J Mater Sci Mater Med 2005; 16(10):933–946.PubMedCrossRefGoogle Scholar
  54. 54.
    Gruner G. Carbon nanotube transistors for biosensing applications. Anal Bioanal Chem 2006; 384(2):322–335.PubMedCrossRefGoogle Scholar
  55. 55.
    Watson P, Jones AT, Stephens DJ. Intracellular trafficking pathways and drug delivery: Fluorescence imaging of living and fixed cells. Adv Drug Deliv Rev 2005; 57(1):43–61.PubMedCrossRefGoogle Scholar
  56. 56.
    Santra S, Zhang P, Wang K et al. Conjugation of biomolecules with luminophore-doped silica nanoparticles for photostable biomarkers. Anal Chem 2001; 73(20):4988–4993.PubMedCrossRefGoogle Scholar
  57. 57.
    Zhao X, Hilliard LR, Mechery SJ et al. A rapid bioassay for single bacterial cell quantitation using bioconjugated nanoparticles. Proc Natl Acad Sci USA 2004; 101(42):15027–15032.PubMedCrossRefGoogle Scholar
  58. 58.
    Stone V, Donaldson K. Nanotoxicology: Signs of stress. Nature Nanotechnology 2006; 1(1):23–24.PubMedCrossRefGoogle Scholar
  59. 59.
    Nel A, Xia T, Madler L et al. Toxic potential of materials at the nanolevel. Science 2006; 311(5761):622–627.PubMedCrossRefGoogle Scholar
  60. 60.
    Derfus AM, Chen WCW, Bhatia SN. Probing the cytotoxicity of semiconductor quantum dots. Nano Letters 2004; 4:11–18.CrossRefGoogle Scholar
  61. 61.
    Lovric J, Cho SJ, Winnik FM et al. Unmodified cadmium telluride quantum dots induce reactive oxygen species formation leading to multiple organelle damage and cell death. Chem Biol 2005; 12(11):1227–1234.PubMedCrossRefGoogle Scholar
  62. 62.
    Kirchner C, Liedl T, Kudera S et al. Cytotoxicity of colloidal CdSe and CdSe/ZnS nanoparticles. Nano Lett 2005; 5(2):331–338.PubMedCrossRefGoogle Scholar
  63. 63.
    Oberdorster E. Manufactured nanomaterials (fullerences, C60) induce oxidative stress in the brain of juvenile largemouth bass. Environ Health Perspect 2004; 112(10):1058–1062.PubMedCrossRefGoogle Scholar
  64. 64.
    Lam CW, James JT, McCluskey R et al. Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation. Toxicol Sci 2004; 77(1):126–134.PubMedCrossRefGoogle Scholar
  65. 65.
    Ipe BI, Lehnig M, Niemeyer CM. On the generation of free radical species from quantum dots. Small 2005; 1(7):706–709.PubMedCrossRefGoogle Scholar
  66. 66.
    Samia AC, Chen X, Burda C. Semiconductor quantum dots for photodynamic therapy. J Am Chem Soc 2003; 125(51):15736–15737.PubMedCrossRefGoogle Scholar
  67. 67.
    Green M, Howman E. Semiconductor quantum dots and free radical induced DNA nicking. Chem Commun (Camb) 2005; (1):121–123.Google Scholar
  68. 68.
    Cho S, Maysinger D, Jain M et al. Long-term exposure to CdTe quantum dots causes functional impairments in live cells. Langmuir 2007; 23(4):1974–1980.PubMedCrossRefGoogle Scholar
  69. 69.
    Toews AD, Lee SY, Popko B et al. Tellurium-induced neuropathy A model for reversible reductions in myelin protein gene expression. J Neurosci Res 1990; 26(4):501–507.PubMedCrossRefGoogle Scholar
  70. 70.
    Moghimi SM, Hunter AC, Murray JC. Nanomedicine: Current status and future prospects. FASEB J 2005; 19(3):311–330.PubMedCrossRefGoogle Scholar
  71. 71.
    Nishiyama N, Kataoka K. Current state, achievements, and future prospects of polymeric micelles as nanocarriers for drug and gene delivery. Pharmacol Ther 2006; 112(3):630–648.PubMedCrossRefGoogle Scholar
  72. 72.
    Xia T, Kovochich M, Brant J et al. Comparison of the abilities of ambient and manufactured nanoparticles to induce cellular toxicity according to an oxidative stress paradigm. Nano Lett 2006; 6(8):1794–1807.PubMedCrossRefGoogle Scholar
  73. 73.
    Noble M, Mayer-Proschel M, Proschel C. Redox regulation of precursor cell function: Insights and paradoxes. Antioxid Redox Signal 2005; 7(11–12):1456–1467.PubMedCrossRefGoogle Scholar
  74. 74.
    Finkel T, Holbrook NJ. Oxidants, oxidative stress and the biology of ageing. Nature 2000; 408(6809):239–247.PubMedCrossRefGoogle Scholar
  75. 75.
    Clarke SJ, Hollmann CA, Zhang Z et al. Photophysics of dopamine-modified quantum dots and effects on biological systems. Nat Mater 2006; 5(5):409–417.PubMedCrossRefGoogle Scholar
  76. 76.
    Hansen JM, Go YM, Jones DP. Nuclear and mitochondrial compartmentation of oxidative stress and redox signaling. Annu Rev Pharmacol Toxicol 2006; 46:215–234.PubMedCrossRefGoogle Scholar
  77. 77.
    Li N, Sioutas C, Cho A et al. Ultrafine particulate pollutants induce oxidative stress and mitochondrial damage. Environ Health Perspect 2003; 111(4):455–460.PubMedGoogle Scholar
  78. 78.
    Broker LE, Kruyt FA, Giaccone G. Cell death independent of caspases: A review. Clin Cancer Res 2005; 11(9):3155–3162.PubMedCrossRefGoogle Scholar
  79. 79.
    Kroemer G, Jaattela M. Lysosomes and autophagy in cell death control. Nat Rev Cancer 2005; 5(11):886–897.PubMedCrossRefGoogle Scholar
  80. 80.
    Xu C, Bailly-Maitre B, Reed JC. Endoplasmic reticulum stress: Cell life and death decisions. J Clin Invest 2005; 115(10):2656–2664.PubMedCrossRefGoogle Scholar
  81. 81.
    Boyce M, Yuan J. Cellular response to endoplasmic reticulum stress: A matter of life or death. Cell Death Differ 2006; 13(3):363–373.PubMedCrossRefGoogle Scholar
  82. 82.
    Zhang K, Kaufman RJ. The unfolded protein response: A stress signaling pathway critical for health and disease. Neurology 2006; 66(2 Suppl 1):S102–109.Google Scholar
  83. 83.
    Oakes SA, Lin SS, Bassik MC. The control of endoplasmic reticulum-initiated apoptosis by the BCL-2 family of proteins. Curr Mol Med 2006; 6(1):99–109.PubMedCrossRefGoogle Scholar
  84. 84.
    Ferri KF, Kroemer G. Organelle-specific initiation of cell death pathways. Nat Cell Biol 2001; 3(11):E255–263.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2007

Authors and Affiliations

  • Dusica Maysinger
    • 1
  • Jasmina Lovrić
    • 1
    • 2
  1. 1.Department of Pharmacology and TherapeuticsMcGill UniversityMontrealCanada
  2. 2.Department of Pharmaceutical TechnologyUniversity of ZagrebZagrebCroatia

Personalised recommendations