Quantum Dot Nanotechnology for Prostate Cancer Research

  • Xiaohu Gao
  • Yun Xing
  • Leland W. K. Chung
  • Shuming Nie
Part of the Contemporary Cancer Research book series (CCR)


Quantum dots (QDs), tiny light-emitting particles on the nanometer scale, are emerging as a new class of fluorescent probes for cancer cell imaging and molecular profiling. In comparison with organic dyes and fluorescent proteins, QDs have unique optical and electronic properties, such as size-tunable light emission, improved signal brightness, resistance against photobleaching, and simultaneous excitation of multiple fluorescence colors. These properties are most promising for improving the sensitivity of molecular imaging and quantitative cellular analysis by one to two orders of magnitude. Recent advances have led to multifunctional nanoparticle probes that are highly bright and stable under complex biological conditions. A new structural design involves encapsulating luminescent QDs with amphiphilic block copolymers, and linking the polymer coating to tumortargeting ligands and drug-delivery functionalities. Polymer-encapsulated QDs are essentially nontoxic to cells and animals, but their long-term in vivo toxicity and degradation need more studies that are careful. Nonetheless, bioconjugated QDs have raised new possibilities for ultrasensitive and multiplexed imaging of molecular targets in living cells, animal models, and, possibly, in human patients.

Key Words

Fluorescence molecular imaging nanotechnology quantum dots tumor targeting 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Chan, W. C. W., Maxwell, D. J., Gao, X. H., Bailey, R. E., Han, M. Y., and Nie, S. M. (2002). Luminescent quantum dots for multiplexed biological detection and imaging. Curr. Opin. Biotechnol. 13, 40–46.PubMedCrossRefGoogle Scholar
  2. 2.
    Han, M. Y., Gao, X. H., Su, J. Z., and Nie, S. M. (2001). Quantum-dot-tagged microbeads for multiplexed optical coding of biomolecules. Nat. Biotechnol. 19, 631–635.PubMedCrossRefGoogle Scholar
  3. 3.
    Gao, X. H. and Nie, S. M. (2003). Doping mesoporous materials with multicolor quantum dots. J. Phys. Chem. B 107, 11,575–11,578.CrossRefGoogle Scholar
  4. 4.
    Gao, X. H. and Nie, S. M. (2004). Quantum dot-encoded mesoporous beads with high brightness and uniformity: rapid readout using flow cytometry. Anal. Chem. 76, 2406–2410.PubMedCrossRefGoogle Scholar
  5. 5.
    Wu, X. Y., Liu, H. J., Liu, J. Q.,et al. (2003). Immunofluorescent labeling of cancer marker Her2 and other cellular targets with semiconductor quantum dots. Nat. Biotechnol. 21, 41–46.PubMedCrossRefGoogle Scholar
  6. 6.
    Dahan, M., Levi, S., Luccardini, C., Rostaing, P., Riveau, B, and Triller, A. (2003). Diffusion dynamics of glycine receptors revealed by single-quantum dot tracking. Science 302, 442–445.PubMedCrossRefGoogle Scholar
  7. 7.
    Lidke, D. S., Nagy, P., Heintzmann, R., et al. (2004). Quantum dot ligands provide new insights into erbB/HER recep-tormediated signal transduction. Nat. Biotechnol. 22, 198–203.PubMedCrossRefGoogle Scholar
  8. 8.
    Xiao, Y. and Barker, P. E. (2004). Semiconductor nanocrystal probes for human metaphase chromosomes. Nucleic Acids Res. 32, e28.PubMedCrossRefGoogle Scholar
  9. 9.
    Jaiswal, J. K., Mattoussi, H., Mauro, J. M., Simon, S. M. (2003). Long-term multiple color imaging of live cells using quantum dot bioconjugates. Nat. Biotechnol. 21, 47–51.PubMedCrossRefGoogle Scholar
  10. 10.
    Medintz, L., Clapp, A. R., Mattoussi, H., Goldman, E. R., Fisher, B., Mauro, J. M. (2003). Self-assembled nanoscale biosensors based on quantum dot FRET donors Igor. Nat. Mat. 2, 630–638.CrossRefGoogle Scholar
  11. 11.
    Medintz, I. L., Konnert, J. H., Clapp, A. R., et al. (2004). A fluorescence resonance energy transfer-derived structure of a quantum dot-protein bioconjugate nanoassembly. Proc. Natl. Acad. Sci. USA 29, 9612–9617.CrossRefGoogle Scholar
  12. 12.
    Rosenthal, S. J., Tomlinson, I., Adkins, E. M., et al. (2002). Targeting cell surface receptors with ligand-conjugated nanocrystals. J. Am. Chem. Soc. 124, 4586–4594.PubMedCrossRefGoogle Scholar
  13. 13.
    Alivisatos, A. P. (1996). Semiconductor clusters, nanocrystals, and quantum dots, Science 271, 933–937.CrossRefGoogle Scholar
  14. 14.
    Alivisatos, A. P. (2004). The use of nanocrystals in biological detection. Nat. Biotechnol. 22, 47–52.PubMedCrossRefGoogle Scholar
  15. 15.
    Manna, L., Milliron, D. J., Meisel, A., Scher, E. C., and Alivisatos, A. P. (2003). Controlled growth of tetrapod branched inorganic nanocrystals. Nat. Mat. 2, 382–385.CrossRefGoogle Scholar
  16. 16.
    Milliron, D. J., Hughes, S. M., Cui, Y., et al. (2004). Colloidal nanocrystal heterostructures with linear and branched topology. Nature 430, 190–195.PubMedCrossRefGoogle Scholar
  17. 17.
    Dick, K. A., Deppert, K., Larsson, M. W., et al. (2004). Synthesis of branched ‘nanotrees’ by controlled seeding of multiple branching events. Nat. Mat. 3, 380–384.CrossRefGoogle Scholar
  18. 18.
    Yu, W. W., Wang, Y. A., and Peng, X. G. (2003). Formation and stability of size-, shape-, and structure-controlled CdTe nanocrystals: Ligand effects on monomers and nanocrystals. Chem. Mat. 15, 4300–4308.CrossRefGoogle Scholar
  19. 19.
    Hines, M. A. and Guyot-Sionnest, P. (1996). Synthesis of strongly luminescing ZnS-capped CdSe nanocrystals. J. Phys. Chem. B 100, 468–471.CrossRefGoogle Scholar
  20. 20.
    Peng, X. G., Schlamp, M. C., Kadavanich, A. V., and Alivisatos, A. P. (1997). Epitaxial growth of highly luminescent CdSe/CdS core/shell nanocrystals with photostability and electronic accessibility. J. Am. Chem. Soc. 119, 7019–7029.CrossRefGoogle Scholar
  21. 21.
    Dabbousi B. O., Rodriguez-Viejo J., Mikulec F. V., et al. (1997). (CdSe)ZnS core-shell quantum dots: synthesis and characterization of a size series of highly luminescent nanocrystallites. J. Phys. Chem. B 101, 9463–9475.CrossRefGoogle Scholar
  22. 22.
    Bailey, R. E. and Nie, S. (2003). Alloyed semiconductor quantum dots: tuning the optical properties without changing the particle size. J. Am. Chem. Soc. 125, 7100–7106.PubMedCrossRefGoogle Scholar
  23. 23.
    Qu, L. H. and Peng, X. G. (2002). Control of photoluminescence properties of CdSe nanocrystals in growth. J. Am. Chem. Soc. 124, 2049–2055.PubMedCrossRefGoogle Scholar
  24. 24.
    Dubertret, B., Skourides, P, Norris, D. J., Noireaux, V., Brivanlou, A. H., Libchaber, A. (2002). In vivo imaging of quantum dots encapsulated in phospholipid micelles. Science 298, 1759–1762.PubMedCrossRefGoogle Scholar
  25. 25.
    Gao, X. H., Cui, Y. Y., Levenson, R. M., Chung, L. W. K., and Nie, S. M. (2004). In vivo cancer targeting and imaging with semiconductor quantum dots. Nat. Biotechnol. 22, 969–976.PubMedCrossRefGoogle Scholar
  26. 26.
    Pellegrino, T., Manna, L., and Kudera, S. (2004). Hydrophobic nanocrystals coated with an amphiphilic polymer shell: a general route to water soluble nanocrystals. Nano. Lett. 4, 703–707.CrossRefGoogle Scholar
  27. 27.
    Ron, E., Turek, T., and Mathiowitz, E. (1993). Controlled release of polypeptides from polyanhydrides. Proc. Natl. Acad. Sci. USA 90, 4176–4180.PubMedCrossRefGoogle Scholar
  28. 28.
    Anseth, K. S., Shastri, V. R., and Langer, R. (1999). Photopolymerizable degradable polyanhydrides with osteocompatibility. Nat. Biotechnol. 17, 156–159.PubMedCrossRefGoogle Scholar
  29. 29.
    Goldman, E. R., Anderson, G. P., Tran, P. T., Mattoussi, H., Charles, P. T., and Mauro, J. M. (2002). Conjugation of luminescent quantum dots with antibodies using an engineered adaptor protein to provide new reagents for fluoroimmunoassays. Anal. Chem. 74, 841–847.PubMedCrossRefGoogle Scholar
  30. 30.
    Leatherdale, C. A., Woo, W. K., Mikulec, F. V., and Bawendi, M. G. (2002). On the absorption cross section of CdSe nanocrystal quantum dots. J. Phys. Chem. B 106, 7619–7622.CrossRefGoogle Scholar
  31. 31.
    Bruchez, J. M., Moronne, M., Gin, P., Weiss, S., and Alivisatos, A. P. (1998). Semiconductor nanocrystals as fluores-cent biological labels. Science 281, 2013–2015.PubMedCrossRefGoogle Scholar
  32. 32.
    Chan, W. C. W. and Nie, S. M. (1998). Quantum dot bioconjugates for ultrasensitive nonisotopic detection. Science 281, 2016–2018.PubMedCrossRefGoogle Scholar
  33. 33.
    Jakobs, S., Subramaniam, V., Schonle, A., Jovin, T. M., and Hell, S. W. (2000). EGFP and DsRed expressing cultures of Escherichia coli imaged by confocal, two-photon and fluorescence lifetime microscopy. FEBS Lett. 479, 131–135.PubMedCrossRefGoogle Scholar
  34. 34.
    Pepperkok, R., Squire, A., Geley, S., and Bastiaens, P. I. H. (1999). Simultaneous detection of multiple green fluores-cent proteins in live cells by fluorescence lifetime imaging microscopy. Curr. Bio. 9 269–272.CrossRefGoogle Scholar
  35. 35.
    Gao, X. H. and Nie, S. M. (2003). Molecular profiling of single cells and tissue specimens with quantum dots. Trends Biotechnol. 21, 371–373.PubMedCrossRefGoogle Scholar
  36. 36.
    Ogawara, K., Yoshida, M., Higaki, K., et al. (1999). Hepatic uptake of polystyrene microspheres in rats: Effect of particle size on intrahepatic distribution. J. Control Release 59, 15–22.PubMedCrossRefGoogle Scholar
  37. 37.
    Flacke, S., Fischer, S., Scott M. J., et al. (2001). Novel MRI contrast agent for molecular imaging of fibrin implications for detecting vulnerable plaques. Circulation 104, 1280–1285.PubMedCrossRefGoogle Scholar
  38. 38.
    Katz, L. C., Burkhalter, A., and Dreyer, W. J. (1984). Fluorescent latex microspheres as a retrograde neuronal marker for in vivo and in vitro studies of visual-cortex. Nature 310, 498–500.PubMedCrossRefGoogle Scholar
  39. 39.
    Chien, G. L., Anselone, C. G., Davis, R. F., and Van Winkle, D. M. (1995). Fluorescent vs. radioactive microsphere measurement of regional myocardial blood flow. Cardiovasc Res. 30, 405–412.PubMedCrossRefGoogle Scholar
  40. 40.
    Pasqualini, R. and Ruoslahti, E. (1996). Organ targeting in vivo using phage display peptide libraries. Nature 380, 364–366.PubMedCrossRefGoogle Scholar
  41. 41.
    Nisman, R., Dellaire, G., Ren, Y., Li, R., and Bazett-Jones, D. P. (2004). Application of quantum dots as probes for correlative fluorescence, conventional, and energy-filtered transmission electron microscopy. J. Histochem. Cytochem. 52, 13–18.PubMedGoogle Scholar
  42. 42.
    Ballou B., Lagerholm B. C., Ernst L. A., Bruchez M. P., and Waggoner A. S. (2004). Noninvasive imaging of quantum dots in mice. Bioconj. Chem. 15, 79–86.CrossRefGoogle Scholar
  43. 43.
    Hoshino A., Hanaki K., Suzuki K., and Yamamoto K. (2004). Applications of T-lymphoma labeled with fluorescent quantum dots to cell tracing markers in mouse body. Biochem. Biophy. Res. Com. 314, 46–53.CrossRefGoogle Scholar
  44. 44.
    Voura E. B., Jaiswal J. K., Mattoussi H., and Simon S. M. (2004). Tracking metastatic tumor cell extravasation with quantum dot nanocrystals and fluorescence emission-scanning microscopy. Nat. Med. 9, 993–998.CrossRefGoogle Scholar
  45. 45.
    Mattheakis L. C., Dias J. M., Choi Y..J, et al. (2004). Optical coding of mammalian cells using semiconductor quantum dots. Anal. Chem. 327, 200–208.Google Scholar
  46. 46.
    Lagerholm, B. C., Wang, M., Ernst, L. A., et al. (2004). Multicolor coding of cells with cationic peptide coated quan-tum dots. Nano Lett. 4(10), 2019–2022.CrossRefGoogle Scholar
  47. 47.
    Lewin, M., Carlesso, N., Tung, C. H., et al. (2000). Tat peptide-derivatized magnetic nanoparticles allow in vivo track-ing and recovery of progenitor cells. Nat. Biotechnol. 18, 410–414.PubMedCrossRefGoogle Scholar
  48. 48.
    Larson, D. R., Zipfel, W. R., Williams, R. M., et al. (2003). Water-soluble quantum dots for multiphoton fluorescence imaging in vivo. Science 300, 1434–1436.PubMedCrossRefGoogle Scholar
  49. 49.
    Stroh, M., Zimmer, J. P., Duda, D. G., et al. (2005). Quantum dots spectrally distinguish multiple species within the tumor milieu in vivo. Nat. Med. 11, 678–682.PubMedCrossRefGoogle Scholar
  50. 50.
    Kim, S., Lim, Y. T., Soltesz, E. G., et al. (2004). Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping. Nat. Biotechnol. 22, 93–97.PubMedCrossRefGoogle Scholar
  51. 51.
    Lim, Y. T., Kim S., Nakayama, A., Stott, N. E., Bawendi, M. G., and Frangioni, J. V. (2003). Selection of quantum dot wavelengths for biomedical assays and imaging. Mol. Imaging 2, 50–64.PubMedCrossRefGoogle Scholar
  52. 52.
    Akerman, M. E., Chan, W. C. W., Laakkonen, P., Bhatia S. N., and Ruoslahti, E. (2002). Nanocrystal targeting in vivo. Proc. Natl. Acad. Sci. USA 99, 12,617–12,621.PubMedCrossRefGoogle Scholar
  53. 53.
    Mattoussi, H., Mauro, J. M., Goldman, E. R., et al. (2000). Self-assembly of CdSe-ZnS quantum dot bioconjugates using an engineered recombinant protein. J. Am. Chem. Soc. 122, 12,142–12,150.CrossRefGoogle Scholar
  54. 54.
    Gao, X. H., Chan, W. C. W., and Nie, S. M. (2002). Quantum-dot nanocrystals for ultrasensitive biological labeling and multicolor optical encoding. J. Biomed. Opt. 7, 532–537.PubMedCrossRefGoogle Scholar
  55. 55.
    Jain, R. K. (1999). Transport of molecules, particles, and cells in solid tumors. Ann. Rev. Biomed. Eng. 1, 241–263.CrossRefGoogle Scholar
  56. 56.
    Jainm R. K. (2001). Delivery of molecular medicine to solid tumors: lessons from in vivo imaging of gene expression and function. J. Control Release 74, 7–25.CrossRefGoogle Scholar
  57. 57.
    Chang, S. S., Reuter, V. E., Heston, W. D. W., and Gaudin, P. B. (2001). Metastatic renal cell carcinoma neovasculature expresses prostate-specific membrane antigen. Urology 57, 801–805.PubMedCrossRefGoogle Scholar
  58. 58.
    Schulke, N., Varlamova, O. A., Donovan, G. P., et al. (2003). The homodimer of prostate-specific membrane antigen is a functional target for cancer therapy. Proc. Natl. Acad. Sci. USA 100, 12,590–12,595.PubMedCrossRefGoogle Scholar
  59. 59.
    Bander, N. H., Trabulsi, E. J., Kostakoglu, L., et al. (2003). Targeting metastatic prostate cancer with radiolabeled monoclonal antibody J591 to the extracellular domain of prostate specific membrane antigen. J. Urol. 170, 1717–1721.PubMedCrossRefGoogle Scholar
  60. 60.
    Derfus, A. M., Chan, W. C. W., and Bhatia, S. N. (2004). Probing the cytotoxicity of semiconductor quantum dots. Nano Lett. 4, 11–18.CrossRefGoogle Scholar
  61. 61.
    Kirchner, C., Liedl, T., Kudera, S., et al. (2005). Cytotoxicity of colloidal CdSe and CdSe/ZnS nanoparticles. Nano Lett. 5, 331–338.PubMedCrossRefGoogle Scholar
  62. 62.
    Wang, D. S., He, J. B., Rosenzweig, N., and Rosenzweig, Z. (2004). Superparamagnetic Fe 2 O 3 Beads-CdSe/ZnS quan-tum dots core-shell nanocomposite particles for cell separation. Nano Lett. 4, 409–413.CrossRefGoogle Scholar
  63. 63.
    Gu, H. W., Zheng, R. K., Zhang, X. X., and Xu, B. (2004). Facile one-pot synthesis of bifunctional heterodimers of nanoparticles: a conjugate of quantum dot and magnetic nanoparticles. J. Am. Chem. Soc. 126, 5664–5665.PubMedCrossRefGoogle Scholar
  64. 64.
    Samia, A. C. S., Chen, X., and Burda, C. (2003). Semiconductor quantum dots for photodynamic therapy. J. Am. Chem. Soc. 125, 15,736–15,737.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 2007

Authors and Affiliations

  • Xiaohu Gao
    • 1
  • Yun Xing
    • 2
  • Leland W. K. Chung
    • 3
  • Shuming Nie
    • 4
  1. 1.Department of BioengineeringUniversity of WashingtonSeattle
  2. 2.Departments of Biomedical Engineering, Chemistry, Hematology and Oncology, and the Winship Cancer InstituteEmory University and Georgia Institute of TechnologyAtlanta
  3. 3.Molecular Urology and Therapeutics Program, Department of Urology, and Winship Cancer InstituteEmory University School of MedicineAtlanta
  4. 4.Departments of Biomedical Engineering, Chemistry, Hematology and Oncology, and the Winship Cancer InstituteEmory University School of Medicine and Georgia Institute of TechnologyAtlanta

Personalised recommendations