Advertisement

Enabling Biomedical Research with Designer Quantum Dots

  • Nikodem TomczakEmail author
  • Dominik Jańczewski
  • Denis Dorokhin
  • Ming-Yong Han
  • G. Julius Vancso
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 811)

Abstract

Quantum Dots (QDs) are a new class of semiconductor nanoparticulate luminophores, which are actively researched for novel applications in biology and nanomedicine. In this review, the recent progress in the design and applications of QD labels for in vitro and in vivo imaging of cells is presented. Surface chemical engineering of hydrophobic QDs is required to render them water soluble and biocompatible. Further surface modification and attachment of bioactive molecules to the surface of QDs, such as peptides, aptamers, or antibodies are intensively explored for targeted imaging of living cells, and disease states in animals. Specially designed surface coatings can drastically decrease nonspecific interactions between QDs and cells, minimize degradation of QDs under in vivo physiological conditions, reduce the cytotoxicity of QDs, and prolong circulation lifetimes in animals. New generations of QD probes are also promising for imaging cellular processes at the single-molecule level. Ultimately, QDs as components of complex therapeutic nanosystems are poised to contribute significantly to the field of personalized medicine.

Key words

Quantum dots Nanocrystals Luminescence Surface modification In vivo imaging Cytotoxicity Cell membrane Endocytosis Living cells 

Notes

Acknowledgments

We are grateful to the Institute of Materials Research and Engineering of A*STAR for financial support.

References

  1. 1.
    Peer, D., Karp, J. M., Hong, S., Farokhzad, O. C., Margalit, R., Langer, R. (2007) Nanocarriers as an emerging platform for cancer therapy. Nature Nanotechnol. 2, 751–760.Google Scholar
  2. 2.
    Iga, A. M., Robertson, J. H. P., Winslet, M. C., Seifalian, A. M. (2007) Clinical potential of quantum dots. J. Biomed. Biotechnol. 2007, 76087.Google Scholar
  3. 3.
    Douma, K., Prinzen, L., Slaaf, D. W., Reutelingsperger, C. P. M., Biessen, E. A. L., Hackeng, T. M., Post, M. J., van Zandvoort, M. A. M. J. (2009) Nanoparticles for optical molecular imaging of atherosclerosis. Small. 5, 544–557.Google Scholar
  4. 4.
    Farokhzad, O. C., Langer, R. (2009) Impact of nanotechnology on drug delivery. ACS Nano. 3, 16–20.Google Scholar
  5. 5.
    Riehemann, K., Schneider, S. W., Luger, T. A., Godin, B., Ferrari, M., Fuchs, H. (2009) Nanomedicine-Challenge and perspectives. Angew. Chem. Int. Ed. 48, 872–897.Google Scholar
  6. 6.
    Alivisatos, P. (2004) The use of nanocrystals in biological detection. Nature Biotechnol. 22, 47–52.Google Scholar
  7. 7.
    Alivisatos, A. P., Gu, W., Larabell, C. (2005) Quantum dots as cellular probes. Annu. Rev. Biomed. Eng. 7, 55-76.Google Scholar
  8. 8.
    Medintz, I. L., Uyeda, H. T., Goldman, E. R., Mattoussi, H. (2005) Quantum dot bioconjugates for imaging, labeling and sensing. Nature Mater. 4, 435–446.Google Scholar
  9. 9.
    Maysinger, D., Lovric, J., Eisenberg, A., Savic, R. (2007) Fate of micelles and quantum dots in cells. Eur. J. Pharma. Biopharma. 65, 270–281.Google Scholar
  10. 10.
    Pathak, S., Cao, E., Davidson, M. C., Jin, S., Silva, G. A. (2006) Quantum dots applications to neuroscience: New tools for probing neurons and glia. J. Neurosc. 26, 1893–1895.Google Scholar
  11. 11.
    Gao, X., Yang, L., Petros, J. A., Marshall, F. F., Simons, J. W., Nie, S. (2005) In vivo molecular and cellular imaging with quantum dots. Curr. Op. Biotechnol. 16, 63–72.Google Scholar
  12. 12.
    Derfus, A. M., Chen, A. A., Min, D.-H., Ruoslahti E., Bhatia S. N. (2007) Targeted quantum dot conjugates for siRNA delivery. Bioconj. Chem. 18, 1391–1396.Google Scholar
  13. 13.
    Lei Y., Tang, H., Yao, L., Yu, R., Fen, M., Zou, B. (2008) Applications of mesenchymal stem cells labeled with Tat peptide conjugated quantum dots to cell tracking in mouse body. Bioconj. Chem. 19, 421–427.Google Scholar
  14. 14.
    Hotz, Charles Z., Bruchez, Marcel (Eds.) (2007) Quantum Dots. Applications in Biology. Methods in Molecular Biology, 374, Humana Press.Google Scholar
  15. 15.
    Reiss, P., Protiere, M., Li, L. (2009) Core/shell semiconductor nanocrystals. Small. 5, 154–168.Google Scholar
  16. 16.
    Resch-Genger, U., Grabolle, M., Cavaliere-Jaricot, S., Nitschke, R., Nann T. (2008) Quantum dots versus organic dyes as fluorescent labels. Nature Meth. 5, 763–775.Google Scholar
  17. 17.
    Bruchez, M., Moronne, M., Gin, P., Weiss, S., Alivisatos, A. P. (1998) Semiconductor nanocrystals as fluorescent biological labels. Science. 281, 2013–2016.Google Scholar
  18. 18.
    Wu, X., Liu, H., Liu, J., Haley, K. N., Treadway, J. A., Larson, J. P., Ge, N., Peale, F., Bruchez, M. P. (2003) Immunofluorescent labeling of cancer marker Her2 and other cellular targets with semiconductor quantum dots. Nature Biotechnol. 21, 41–46.Google Scholar
  19. 19.
    Jaiswal, J. K., Mattoussi, H., Mauro, J. M., Simon, S. M. (2003) Long-term multiple color imaging of live cells using quantum dot bioconjugates. Nature Biotechnol. 21, 47–51.Google Scholar
  20. 20.
    Yezhelyev, M. V., Al-Hajj, A., Morris, C., Marcus, A. I., Liu, T., Lewis, M., Cohen, C., Zrazhevskiy, P., Simons, J. W., Rogatko, A., Nie, S., Gao, X., O’Regan, R. M. (2007) In situ molecular profiling of breast cancer biomarkers with multicolor quantum dots. Adv. Mater. 19, 3146–3151.Google Scholar
  21. 21.
    Chen, I., Choi, Y.-A., Ting, A. Y. (2007) Phage display evolution of a peptide substrate for yeast biotin ligase and application to two-color quantum dot labeling of cell surface proteins. J. Am. Chem. Soc. 129, 6619–6625.Google Scholar
  22. 22.
    Lidke, D. S., Nagy, P., Heintzmann, R., Arndt-Jovin, D. J., Post, J. N., Grecco, H. E., Jares-Erijman, E. A., Jovin T. M. (2004) Quantum dot ligands provide new insights into erbB/HER receptor-mediated signal transduction. Nature Biotechnol. 22, 198–203.Google Scholar
  23. 23.
    Han, M., Gao, X., Su, J. Z., Nie, S. (2001) Quantum-dot-tagged microbeads for multiplexed optical coding of biomolecules. Nature Biotechnol. 19, 631–635.Google Scholar
  24. 24.
    Lagerholm, B. C., Wang, M., Ernst, L. A., Ly, D. H., Liu, H., Bruchez, M. P., Waggoner, A. S. (2004) Multicolor coding of cells with cationic peptide coated quantum dots. Nano Lett. 4, 2019–2022.Google Scholar
  25. 25.
    Mattheakis, L. C., Dias, J. M., Choi, Y.-J., Gong, J., Bruchez, M. P., Liu, J., Wang, E. (2004) Optical coding of mammalian cells using semiconductor quantum dots. Anal. Biochem. 327, 200-208.Google Scholar
  26. 26.
    Voura, E. B., Jaiswal, J. K., Mattoussi, H., Simon, S. M. (2004) Tracking metastatic tumor cell extravasation with quantum dot nanocrystals and fluorescence emission-scanning microscopy. Nature Med. 10, 993–998.Google Scholar
  27. 27.
    Ballou, B., Lagerholm, B. C., Ernst, L. A., Bruchez, M. P., Waggoner, A. S. (2004) Noninvasive imaging of quantum dots in mice. Bioconj. Chem. 5, 79–86.Google Scholar
  28. 28.
    Michalet, X., Pinaud, F. F., Bentolila, L. A., Tsay, J. M., Doose, S., Li, J. J., Sundaresan, G., Wu, A. M., Gambhir, S. S., Weiss, S. (2005) Quantum dots for live cells, in vivo imaging, and diagnostics. Science. 307, 538–544.Google Scholar
  29. 29.
    Parak, W. J., Boudreau, R., Le Gros, M., Gerion, D., Zanchet, D., Micheel, C. M., Williams, S. C., Alivisatos, A. P., Larabell, C. (2002) Cell motility and metastatic potential studies based on quantum dot imaging of phagokinetic tracks. Adv. Mater. 14, 882–885.Google Scholar
  30. 30.
    Kim, S., Lim, Y. T., Soltesz, E. G., De Grand, A. M., Lee, J., Nakayama, A., Parker, J. A., Mihaljevic, T., Laurence, R. G., Dor, D. M., Cohn, L. H., Bawendi, M. G., Frangioni, J. V. (2004) Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping. Nature Biotechnol. 22, 93–97.Google Scholar
  31. 31.
    Jaiswal, J. K., Simon, S. M. (2007) Imaging single events at the cell membrane. Nature Chem. Biol. 3, 92–98.Google Scholar
  32. 32.
    Durisic, N., Bachir, A. I., Kolin, D. L., Hebert, B., Lagerholm, B. C., Grutter, P., Wiseman, P. W. (2007) Detection and correction of blinking bias in image correlation transport measurements of quantum dots tagged macromolecules. Biophys. J. 93, 1338–1346.Google Scholar
  33. 33.
    Iyer, G., Michalet, X., Chang, Y.-P., Pinaud, F. F., Matyas, S. E., Payne, G., Weiss, S. (2008) High affinity scFv-hapten pair as a tool for quantum dot labeling and tracking of single proteins in live cells. Nano Lett. 8, 4618–4623.Google Scholar
  34. 34.
    Lieleg, O., Lopez-Garcia, M., Semmrich, C., Auernheimer, J., Kessler, H., Bausch, A. R. (2007) Specific integrin labeling in living cells using functionalized nanocrystals. Small. 3, 1560–1565.Google Scholar
  35. 35.
    Zhou, M., Nakatami, E., Gronenberg, L. S., Tokimoto, T., Wirth, M. J., Hruby, V. J., Roberts, A., Lynch, R. M., Ghosh, I. (2007) Peptide-labeled quantum dots for imaging GPCRs in whole cells and as single molecules. Bioconj. Chem. 18, 323–332.Google Scholar
  36. 36.
    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, 442–445.Google Scholar
  37. 37.
    Nan, X., Sims, P. A., Chen, P., Xie, X. S. (2005) Observation of individual microtubule motor steps in living cells with endocytosed quantum dots. J. Phys. Chem. B 109, 24220–24224.Google Scholar
  38. 38.
    Courty, S., Luccardini, C., Bellaiche, Y., Cappello, G., Dahan, M. (2006) Tracking individual kinesin motors in living cells using single quantum-dot imaging. Nano Lett. 6, 1491–1495.Google Scholar
  39. 39.
    Bannai, H., Levi, S., Schweizer, C., Dahan, M., Triller, A. (2006) Imaging the lateral diffusion of membrane molecules with quantum dots. Nature Protocols. 1, 2628–2634.Google Scholar
  40. 40.
    Roullier, V., Clarke, S., You, C., Pinaud, F., Gouzer, G., Schaible, D., Marchi-Artzner, V., Piehler, J., Dahan, M. (2009) High-affinity labeling and tracking of individual histidine-tagged proteins in live cells using Ni2+ tris-nitrilotriacetic acid quantum dot conjugate. Nano Lett. 9, 1228–1234.Google Scholar
  41. 41.
    Holtzer, L., Meckel, T., Schmidt, T. (2007) Nanometric three-dimensional tracking of individual quantum dots in cells. Appl. Phys. Lett. 90, 053902.Google Scholar
  42. 42.
    Nirmal, M., Dabbousi, B. O., Bawendi, M. G., Macklin, J. J., Trautman, J. K., Harris, T. D., Brus, L. E. (1996) Fluorescence intermittency in single cadmium selenide nanocrystals. Nature. 383, 802–804.Google Scholar
  43. 43.
    Empedocles, S. A., Neuhauser, R., Shimizu, K., Bawendi, M. G. (1999) Photoluminescence from single semiconductor nanostructures. Adv. Mater. 11, 1243–1256.Google Scholar
  44. 44.
    Spinicelli, P., Mahler, B., Buil, S., Quelin, X., Dubertret, B., Hermier, J.-P. (2009) Non-blinking semiconductor colloidal quantum dots for biology, optoelectronics and quantum optics. ChemPhysChem. 10, 879–882.Google Scholar
  45. 45.
    Smith, A. M., Nie, S. (2009) Next-generation quantum dots. Nature Biotechnol. 27, 732–733.Google Scholar
  46. 46.
    Fernandez-Suarez, M., Ting, A. Y. (2008) Fluorescent probes for super-resolution imaging in living cells. Nature Rev. Mol. Cell Biol. 9, 929–943.Google Scholar
  47. 47.
    Yong, K.-T., Qian, J., Roy, I., Lee, H. H., Bergey, E. J., Tramposch, K. M., He, S., Swihart, M. T., Maitra, A., Prasad, P. N. (2007) Quantum rod bioconjugates as targeted probes for confocal and two-photon fluorescence imaging of cancer cells. Nano Lett. 7, 761–765.Google Scholar
  48. 48.
    Fu, A., Gu, W., Boussert, B., Koski, K., Gerion, D., Manna, L., Le Gros, M., Larabell, C. A., Alivisatos, A. P. (2007) Semiconductor quantum rods as single molecule fluorescent biological labels. Nano Lett. 7, 179–182.Google Scholar
  49. 49.
    Yong, K.-T., Roy, I., Pudavar, H. E., Bergey, E. J., Tramposch, K. M., Swihart, M. T., Prasad, P. N. (2008) Multiplex imaging of pancreatic cancer cells by using functionalized quantum rods. Adv. Mater. 20, 1412–1417.Google Scholar
  50. 50.
    Deka, S., Quarta, A., Lupo, M. G., Falqui, A., Boninelli, S., Giannini, C., Morello, G., De Giorgi, M., Lanzani, G., Spinella, C., Cingolani, R., Pellegrino, T., Manna, L. (2009) CdSe/CdS/ZnS double shell nanorods with high photoluminescence efficiency and their exploitation as biolabeling probes. J. Am. Chem. Soc. 131, 2948–2958.Google Scholar
  51. 51.
    Quarta, A., Ragusa, A., Deka, S., Tortiglione, C., Tino, A., Cingolani, R., Pellegrino, T. (2009) Bioconjugation or rod-shaped fluorescent nanocrystals for efficient targeted cell labeling. Langmuir. 25, 12614–12622.Google Scholar
  52. 52.
    Tomczak, N., Jańczewski, D., Han, M.-Y., Vancso, G. J. (2009) Designer polymer-quantum dot architectures. Progr. Polym. Sci. 34, 393–430.Google Scholar
  53. 53.
    Hines, M. A., Guyot-Sionnest, P. (1996) Synthesis and characterization of strongly luminescing ZnS-capped CdSe nanocrystals. J. Phys. Chem. 100, 468–471.Google Scholar
  54. 54.
    Peng, X., Schlamp, M. C., Kadavanich, A. V., 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.Google Scholar
  55. 55.
    Mulvaney, P., Liz-Marzán, L. M., Giersig, M., Ung, T. (2000) Silica encapsulation of quantum dots and metal clusters. J. Mater. Chem. 10, 1259–1270.Google Scholar
  56. 56.
    Gerion, D., Pinaud, F., Williams, S. C., Parak, W. J., Zanchet, D., Weiss, S., Alivisatos, A. P. (2001) Synthesis and properties of biocompatible water soluble silica-coated CdSe/ZnS semiconductor quantum dots. J. Phys. Chem. B 105, 8861–8871.Google Scholar
  57. 57.
    Darbandi, M., Thomann, R., Nann, T. (2005) Single quantum dots in silica spheres by microemulsion synthesis. Chem. Mater. 17, 5720–5725.Google Scholar
  58. 58.
    Zhu, M.-Q., Chang, E., Sun, J., Drezek, R. A. (2007) Surface modification and functionalization of semiconductor quantum dots through reactive coating of silanes in toluene. J. Mater. Chem. 17, 800–805.Google Scholar
  59. 59.
    Parak, W. J., Gerion, D., Zanchet, D., Woerz, A. S., Pellegrino, T., Micheel, C., Williams, S. C., Seitz, M., Bruehl, R. E., Bryant, Z., Bustamante, C., Bertozzi, C. R., Alivisatos, A. P. (2002) Conjugation of DNA to silanized colloidal semiconductor nanocrystalline quantum dots. Chem. Mater. 14, 2113–2119.Google Scholar
  60. 60.
    Schroedter, A., Weller, H., Eritja, R., Ford, W. E., Wessels, J. M. (2002) Biofunctionalization of silica-coated CdTe and gold nanocrystals. Nano Lett. 2, 1363–1367.Google Scholar
  61. 61.
    Selvan, S. T., Tan, T. T., Ying, J. Y. (2005) Robust, non-cytotoxic, silica-coated CdSe quantum dots with efficient photoluminescence. Adv. Mater. 17, 1620–1625.Google Scholar
  62. 62.
    Chan, W. C. W., Nie, S. (1998) Quantum dot bioconjugates for ultrasensitive nonisotopic detection. Science 281, 2016–2018.Google Scholar
  63. 63.
    Tomczak, N., Jańczewski, D., Tagit, O., Han, M. Y., Vancso, G. J. Surface engineering of quantum dots with designer ligands. In Surface Design: Applications in Bioscience and Nanotechnology. Förch, R., Schönherr, H., Jenkins, A. T. A. Eds. Wiley, 2009.Google Scholar
  64. 64.
    Susumo, K., Mei, B. C., Mattoussi, H. (2009) Multifunctional ligands based on dihydrolipoic acid and polyethylene glycol to promote biocompatibility of quantum dots. Nature Protocols 4, 424–436.Google Scholar
  65. 65.
    Mei, B. C., Susumu, K., Medintz, I. L., Mattoussi, H. (2009) Polyethylene glycol-based bidentate ligands to enhance quantum dot and gold nanoparticle stability in biological media. Nature Protocols. 4, 412–423.Google Scholar
  66. 66.
    Carion, O., Mahler, B., Pons, T., Dubertret, B. (2007) Synthesis, encapsulation, purification and coupling of single quantum dots in phospholipid micelles for their use in cellular and in vivo imaging. Nature Protocols. 2, 2383– 2390.Google Scholar
  67. 67.
    Lin, C.-A. J., Sperling, R. A., Li, J. K., Yang, T.-Y., Li, P.-Y., Zanella, M., Chang, W. H., Parak, W. J. (2008) Design of an amphiphilic polymer for nanoparticle coating and functionalization. Small 4, 334–341.Google Scholar
  68. 68.
    Pellegrino, T., Manna, L., Kudera, S., Liedl, T., Koktysh, D., Rogach, A. L., Keller, S., Radler, J., Natile, G., Parak, W. J. (2004) Hydrophobic nanocrystals coated with an amphiphilic polymer shell: A general route to water soluble nanocrystals. Nano Lett. 4, 703–707.Google Scholar
  69. 69.
    Gao, X., Cui, Y., Levenson, R. M., Chung, L. W. K., Nie, S. (2004) In vivo cancer targeting and imaging with semiconductor quantum dots. Nature Biotechnol. 22, 969–976.Google Scholar
  70. 70.
    Jańczewski, D., Tomczak, N., Khin, Y. W., Han, M. Y. Vancso, G. J. (2009) Designer multi-functional comb-polymers for surface engineering of quantum dots on the nanoscale. Eur. Polym. J. 45 (1), 3–9.Google Scholar
  71. 71.
    Yang, L., Mao, H., Wang, Y. A., Cao, Z., Peng, X., Wang, X., Duan, H., Ni, C., Yuan, Q., Adams, G., Smith, M. Q., Wood, W. C., Gao, X., Nie, S. (2009) Single chain epidermal growth factor receptor antibody conjugated nanoparticles for in vivo tumor targeting and imaging. Small. 5, 235–243.Google Scholar
  72. 72.
    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.Google Scholar
  73. 73.
    Jańczewski, D., Tomczak, N., Liu S. H., Han, M. Y., Vancso G. J. (2010) Covalent assembly of functional inorganic nanoparticles by “click” chemistry in water. Chem. Commun. 46 (19), 3253–3255.Google Scholar
  74. 74.
    Mulder, W. J. M., Koole, R., Brandwijk, R. J., Storm, G., Chin, P. T. K., Strijkers, G. J., de Mello Donega, C., Nicolay, K., Griffioen, A. W. (2006) Quantum dots with a paramagnetic coating as a bimodal molecular imaging probe. Nano Lett. 6, 1–6.Google Scholar
  75. 75.
    Bakalova, R., Zhelev, Z., Aoki, I., Kanno, I. (2007) Designing quantum-dot probes. Nature Photonics 1, 487–489.Google Scholar
  76. 76.
    Wang, S., Jarrett, B. R., Kauzlarich, S. M., Louie, A. Y. (2007) Core/shell quantum dots with high relaxivity and photoluminescence for multimodality imaging. J. Am. Chem. Soc. 129, 3848–3856.Google Scholar
  77. 77.
    Cormode, D. P., Skajaa, T., van Schooneveld, M. M., Koole, R., Jarzyna, P., Lobatto, M. E., Calcagno, C., Barazza, A., Gordon, R. E., Zanzonico, P., Fisher, E. A., Fayad, Z. A., Mulder, W. J. M. (2008) Nanocrystal core high-density lipoproteins: A multimodality contrast agent platform. Nano Lett. 8, 3715–3723.Google Scholar
  78. 78.
    Bruns, O. T., Ittrich, H., Peldschus, K., Kaul, M. G., Tromsdorf, U. I., Lauterwasser, J., Nikolic, M. S., Mollwitz, B., Merkel, M., Bigall, N. C., Sapra, S., Reimer, R., Hohenberg, H., Weller, H., Eychmuller, A., Adam, G., Beisiegel, U., Heeren, J. (2009) Real-time magnetic resonance imaging and quantification of lipoprotein metabolism in vivo using nanocrystals. Nature Nanotechnol. 4, 193–201.Google Scholar
  79. 79.
    Duconge F., Pons, T., Pestourie, C., Herin, L., Theze, B., Gombert, K., Mahler, B., Hinnen, F., Kuhnast, B., Dolle, F., Dubertret, B., Tavitian, B. (2008) Fluorine-18-labeled phospholipid quantum dot micelles for in vivo multimodal imaging from whole body to cellular scales. Bioconj. Chem. 19, 1921–1926.Google Scholar
  80. 80.
    Schipper, M. L., Cheng, Z., Lee, S. W., Bentolila, L. A., Iyer, G., Rao, J. H., Chen, X. Y., Wul, A. M., Weiss, S., Gambhir, S. S. (2007) MicroPET-based biodistribution of quantum dots in living mice. J. Nucl. Med. 48, 1511–1518.Google Scholar
  81. 81.
    Nel, A., Xia, T., Li, N. (2006) Toxic potential of materials at the nanolevel. Science 311, 622–627.Google Scholar
  82. 82.
    Nel, A. E., Madler, L., Velegol, D., Xia, T., Hoek, E. M. V., Somasundaran, P., Klaessig, F., Castranova, V., Thompson, M. (2009) Understanding biophysicochemical interactions at the nano-bio interface. Nature Mater. 8, 543–557.Google Scholar
  83. 83.
    Hussain, S. M., Braydich-Stolle, L. K., Schrand, A. M., Murdock, R. C., Yu, K. O., Mattie, D. M., Schlager, J. J., Terrones, M. (2009) Toxicity evaluation for safe use of nanomaterials: Recent achievements and technical challenges. Adv. Mater. 21, 1549–1559.Google Scholar
  84. 84.
    Derfus, A. M., Chan, W. C. W., Bhatia, S. N. (2004) Probing the cytotoxicity of semiconductor quantum dots. Nano Lett. 4, 11–18.Google Scholar
  85. 85.
    Kirchner, C., Liedl, T., Kudera, S., Pellegrino T., Munoz Javier, A., Gaub, H. E., Stolzle, S., Fertig, N., Parak, W. J. (2005) Cytotoxicity of colloidal CdSe and CdSe/ZnS nanoparticles. Nano Lett. 5, 331–338.Google Scholar
  86. 86.
    Lovric, J., Bazzi, H. S., Cuie, Y., Fortin, G. R. A., Winnik, F. M., Maysinger, D. (2005) Differences in subcellular distribution and toxicity of green and red emitting CdTe quantum dots. J. Mol. Med. 83, 377–385.Google Scholar
  87. 87.
    Alsharif, N. H., Berger, C. E. M., Varanasi, S. S., Chao, Y., Horrocks, B. R., Datta, H. K. (2009) Alkyl-capped silicon nanocrystals lack cytotoxicity and have enhanced intracellular accumulation in malignant cells via cholesterol-dependent endocytosis. Small 5, 221–228.Google Scholar
  88. 88.
    Bharali, D. J., Lucey, D. W., Jayakumar, H., Pudavar, H. E., Prasad, P. N. (2005) Folate-receptor-mediated delivery of InP quantum dots for bioimaging using confocal and two-photon microscopy. J. Am. Chem. Soc. 127, 11364–11371.Google Scholar
  89. 89.
    Hussain, S., Won, N., Nam, J., Bang, J., Chung, H., Kim, S. (2009) One-pot fabrication of high-quality InP/ZnS (core/shell) quantum dots and their application to cellular imaging. ChemPhysChem. 10, 1466–1470.Google Scholar
  90. 90.
    Hoshino, A., Fujioka, K., Oku, T., Suga, M., Sasaki, Y. F., Ohta, T., Yasuhara, M., Suzuki, K., Yamamoto, K. (2004) Physicochemical properties and cellular toxicity of nanocrystal quantum dots depend on their surface modification. Nano Lett. 4, 2163–2169.Google Scholar
  91. 91.
    Jiang, W., Kim, B. Y. S., Rutka, J. T., Chan, W. C. W. (2008) Nanoparticle-mediated cellular response is size-dependent. Nature Nanotechnol. 3, 145–150.Google Scholar
  92. 92.
    Liu, W., Choi, H. S., Zimmer, J. P., Tanaka, E., Frangioni, J. V., Bawendi, M. (2007) Compact cysteine-coated CdSe(ZnCdS) quantum dots for in vivo applications. J. Am. Chem. Soc. 129, 14530–14531.Google Scholar
  93. 93.
    Liu, W., Howarth, M., Greytak, A. B., Zheng, Y., Nocera, D. G., Ting, A. Y., Bawendi, M. G. (2008) Compact biocompatible quantum dots functionalized for cellular imaging. J. Am. Chem. Soc. 130, 1274–1284.Google Scholar
  94. 94.
    Howarth, M., Liu, W., Puthenveetil, S., Zheng, Y., Marshall, L. F., Schmidt, M. M., Wittrup, K. D., Bawendi, M. G., Ting, A. Y. (2008) Monovalent, reduced-size quantum dots for imaging receptors on living cells. Nature Meth. 5, 397–399.Google Scholar
  95. 95.
    Zaman, M. B., Baral, T. N., Zhang, J., Whitfield, D., Yu, K. (2009) Single-domain antibody functionalized CdSe/ZnS quantum dots for cellular imaging of cancer cells. J. Phys. Chem. C 113, 496–499.Google Scholar
  96. 96.
    Chang, E., Thekkek, N., Yu, W. W., Colvin, V. L., Drezek, R. (2006) Evaluation of quantum dot cytotoxicity based on intracellular uptake. Small. 2, 1412–1417.Google Scholar
  97. 97.
    Tarantola, M., Schneider, D., Sunnick, E., Adam, H., Pierrat, S., Rosman, C., Breus, V., Sonnichsen, C., Basche, T., Wegener, J., Janshoff, A. (2009) Cytotoxicity of metal and semiconductor nanoparticles indicated by cellular micromotility. ACS Nano. 3, 213–222.Google Scholar
  98. 98.
    Ipe, B. I., Lehnig, M., Niemeyer, C. M. (2005) On the generation of free radical species from quantum dots. Small. 1, 706–709.Google Scholar
  99. 99.
    Samia, A. C. S., Chen, X., Burda, C. (2003) Semiconductor quantum dots for photodynamic therapy. J. Am. Chem. Soc. 125, 15736–15737.Google Scholar
  100. 100.
    Bakalova, R., Ohba, H., Zhelev, Z., Nagase, T., Jose, R., Ishikawa, M., Baba, Y. (2004) Quantum dot anti-CD conjugates: Are they potential photosensitizers or potentiators of classical photosensitizing agents in photodynamic therapy of cancer? Nano Lett. 4, 1567–1573.Google Scholar
  101. 101.
    Tsay, J. M., Trzoss, M., Shi, L., Kong, X., Selke, M., Jung, M. E., Weiss, S. (2007) Singlet oxygen production by peptide-coated quantum dot-photosensitizer conjugates. J. Am. Chem. Soc. 129, 6865–6871.Google Scholar
  102. 102.
    Mattoussi, H., Mauro, J. M., Goldman, E. R., Anderson, G. P., Sundar, V. C., Mikulec, F. V., Bawendi, M. G. (2000) Self-assembly of CdSe-ZnS quantum dot bioconjugates using an engineered recombinant protein. J. Am. Chem. Soc. 122, 12142–12150.Google Scholar
  103. 103.
    Goldman, E. R., Balighian, E. D., Mattoussi, H., Kuno, M. K., Mauro, J. M., Tran, P. T., Anderson, G. P. (2002) Avidin: A natural bridge for quantum dot-antibody conjugates. J. Am. Chem. Soc. 124, 6378–6382.Google Scholar
  104. 104.
    Jaiswal, J. K., Goldman, E. R., Mattoussi, H., Simon, S. M. (2004) Use of quantum dots for live cell imaging. Nature Methods. 1, 73–78.Google Scholar
  105. 105.
    Bhang, S. K., Won, N., Lee, T.-J., Jin, H., Nam, J., Park, J., Chung, H., Park, H.-S., Sung, Y.-E., Hahn, S. K., Kim, B.-S., Kim., S. (2009) Hyaluronic acid-quantum dot conjugates for in vivo lymphatic vessel imaging. ACS Nano. 3, 1389–1398.Google Scholar
  106. 106.
    Akerman, M. E., Chan, W. C. W., Laakkonen, P., Bhatia, S. N., Ruoslahti, E. (2002) Nanocrystals targeting in vivo. Proc. Natl. Acad. Sci. USA. 99, 12617–12621.Google Scholar
  107. 107.
    Pinaud, F., King, D., Moore, H.-P., Weiss, S. (2004) Bioactivation and cell targeting of semiconductor CdSe/ZnS nanocrystals with phytochelatin-related peptides. J. Am. Chem. Soc. 126, 6115–6123.Google Scholar
  108. 108.
    Delehanty, J. B., Medintz, I. L., Pons, T., Brunel, F. M., Dawson, P. E., Mattoussi, H. (2006) Self-assembled quantum dot-peptide bioconjugates for selective intracellular delivery. Bioconj. Chem. 17, 920–927.Google Scholar
  109. 109.
    Winter, J. O., Liu, T. Y., Korgel, B. A., Schmidt, C. E. (2001) Recognition molecule directed interfacing between semiconductor quantum dots and nerve cells. Adv. Mater. 13, 1673–1677.Google Scholar
  110. 110.
    Xing, Y., Chaudry, Q., Shen, C., Kong, K. Y., Zhau, H. E., Chung, L. W., Petros, J. A., O’Regan, R. M., Yezhelyev, M. V., Simons, J. W., Wang, M. D. (2007) Bioconjugated quantum dots for multiplexed and quantitative immunohistochemistry. Nature Protocols. 2, 1152–1165.Google Scholar
  111. 111.
    Rosenthal, S. J., Tomlinson, I., Adkins, E. M., Schroeter, S., Adams, S., Swafford, L., McBride, J., Wang, Y., DeFelice, L. J., Blakely, R. D. (2002) Targeting cell surface receptors with ligand-conjugated nanocrystals. J. Am. Chem. Soc. 124, 4586–4594.Google Scholar
  112. 112.
    Chen, X.-C., Deng, Y.-L., Lin, Y., Pang, D.-W., Qing, H., Qu, F., Xie, H.-Y. (2008) Quantum dot-labeled aptamer nanoprobes specifically targeting glioma cells. Nanotechnology. 19, 235105.Google Scholar
  113. 113.
    Khorev, O., Stokmaier, D., Schwardt, O., Cutting, B., Ernst, B. (2008) Trivalent, Gal/GalNAc-containing ligands designed for the asialoglycoprotein receptor. Bioorg. Med. Chem. 16, 5216–5231.Google Scholar
  114. 114.
    Kikkeri, R., Lepenies, B., Adibekian, A., Laurino, P., Seeberger, P.H. (2009) In vitro imaging and in vivo liver targeting with carbohydrate capped quantum dots. J. Am. Chem. Soc. 131, 2110–2112.Google Scholar
  115. 115.
    Babu, P., Sinha, S., Surolia, A. (2007) Sugar-quantum dot conjugates for a selective and sensitive detection of lectins. Bioconj. Chem. 18, 146–151.Google Scholar
  116. 116.
    Howarth, M., Takao, K., Hayashi, Y., Ting, A. Y. (2005) Targeting quantum dots to surface proteins in living cells with biotin ligase. Proc. Natl. Acad. Soc. USA. 102, 7583–7588.Google Scholar
  117. 117.
    Gussin, H. A., Tomlinson, I. D., Little, D. M., Warnement, M. R., Qian, H., Rosenthal, S. J., Pepperberg, D. R. (2006) Binding of muscimol-conjugated quantum dots to GABAc receptors. J. Am. Chem. Soc. 128, 15701–15713.Google Scholar
  118. 118.
    Rajan, S. S., Vu, T. Q. (2006) Quantum dots monitor TrkA receptor dynamics in the interior of neural PC12 cells. Nano Lett. 6, 2049.Google Scholar
  119. 119.
    Luccardini, C., Yakovlev, A., Gaillard, S., Vant Hoff, M., Alberola, A. P., Mallet, J.-M., Parak, W. J., Feltz, A., Oheim, M. (2007) Getting across the plasma membrane and beyond: intracellular uses of colloidal semiconductor nanocrystals. J. Biomed. Biotechnol. 2007, 68963.Google Scholar
  120. 120.
    Chen, F., Gerion, D. (2004) Fluorescent CdSe/ZnS nanocrystal-peptide conjugates for long-term, nontoxic imaging and nuclear targeting in living cells. Nano Lett. 4, 1827–1832.Google Scholar
  121. 121.
    Ruan, G., Agrawal, A., Marcus, A. I., Nie, S. (2007) Imaging and tracking of Tat peptide-conjugated quantum dots in living cells: New insights into nanoparticle uptake, intracellular transport, and vesicle shedding. J. Am. Chem. Soc. 129, 14759–14766.Google Scholar
  122. 122.
    Medintz, I. L., Pons, T., Delehanty, J. B., Susumu, K., Brunel, F. M., Dawson, P. E., Mattoussi, H. (2008) Intracellular delivery of quantum dot-protein cargos mediated by cell penetrating peptides. Bioconj. Chem. 19, 1785–1795.Google Scholar
  123. 123.
    Anas, A., Okuda, T., Kawashima, N., Nakayama, K., Itoh, T., Ishikawa, M., Biju, V. (2009) Clathrin-mediated endocytosis of quantum dot-peptide conjugates in living cells. ACS Nano. 3, 2419–2429.Google Scholar
  124. 124.
    Delehanty, J. B., Mattoussi, H., Medintz, I. L. (2009) Delivering quantum dots into cells: strategies, progress and remaining issues. Anal. Bioanal. Chem. 393, 1091–1105.Google Scholar
  125. 125.
    Zhang, Y., So, M. K., Rao, J. (2006) Protease-modulated cellular uptake of quantum dots. Nano Lett. 6, 1988–1992.Google Scholar
  126. 126.
    Mok, H., Bae, K. H., Ahn, C.-H., Park, T. G. (2008) PEGylated and MMP-2 specifically dePEGylated quantum dots: Comparative evaluation of cellular uptake. Langmuir. 25, 1645–1650.Google Scholar
  127. 127.
    Barua, S., Rege, K. (2009) Cancer-cell-phenotype-dependent differential intracellular trafficking of unconjugated quantum dots. Small. 5, 370–376.Google Scholar
  128. 128.
    Duan, H., Nie, S. (2007) Cell-penetrating quantum dots based on multivalent and endosome-disrupting surface coatings. J. Am. Chem. Soc. 129, 3333–3338.Google Scholar
  129. 129.
    Xue, F. L., Chen, J. Y., Guo, J., Wang, C. C., Yang, W. L., Wang, P. N., Lu, D. R. (2007) Enhancement of intracellular delivery of CdTe quantum dots (QDs) to living cells by Tat conjugation. J. Fluoresc. 17, 149–154.Google Scholar
  130. 130.
    Jablonski, A. E., Humphries IV, W. H., Payne, C. K. (2009) Pyrenebutyrate-mediated delivery of quantum dots across the plasma membrane of living cells. J. Phys. Chem. B 113, 405–408.Google Scholar
  131. 131.
    Biju, V., Muraleedharan, D., Nakayama, K., Shinohara, Y., Itoh, T., Baba, Y., Ishikawa, M. (2007) Quantum dot-insect neuropeptide conjugates for fluorescence imaging, transfection, and nucleus targeting of living cells. Langmuir. 23, 10254–10261.Google Scholar
  132. 132.
    Ballou, B., Ernst, L. A., Andreko, S., Harper, S., Fitzpatrick, J. A. J., Waggoner, A. S., Bruchez, M. P. (2007) Sentinel lymph node imaging using quantum dots in mouse tumor models. Bioconj. Chem. 18, 389–396.Google Scholar
  133. 133.
    Larson, D. R., Zipfel, W. R., Williams, R. M., Clark, S. W., Bruchez, M. P., Wise, F. W., Webb, W. W. (2003) Water-soluble quantum dots for multiphoton fluorescence imaging in vivo. Science. 300, 1434–1436.Google Scholar
  134. 134.
    Dong, W., Guo, L., Xu, S. (2009) CdTe QDs-based prostate-specific antigen probe for human prostate cancer cell imaging. J. Lumin. 129, 926–930.Google Scholar
  135. 135.
    Yong, K.-T., Ding, H., Roy, I., Law, W.-C., Bergey, E. J., Maitra, A., Prasad, P. N. (2009) Imaging pancreatic cancer using bioconjugated InP quantum dots. ACS Nano. 3, 502–510.Google Scholar
  136. 136.
    Yong, K.-T., Roy, I., Ding, H., Bergey, E. J., Prasad, P. N. (2009) Biocompatible near-infrared quantum dots as ultrasensitive probes for long-term in vivo imaging applications. Small. 5, 1997–2004.Google Scholar
  137. 137.
    So, M.-K., Xu, C., Loening, A. M., Gambhir, S. S., Rao, J. (2006) Self-illuminating quantum dot conjugates for in-vivo imaging. Nature Biotechnol. 24, 339–343.Google Scholar
  138. 138.
    Gomez, N., Winter, J. O., Shieh, F., Saunders, A. E., Korgel, B. A., Schmidt, C. E. (2005) Challenges in quantum dot-neuron active interfacing. Talanta. 67, 462–471.Google Scholar
  139. 139.
    Vu, T. Q., Maddipati, R., Blute, T. A., Nehilla, B. J., Nusblat, L., Desai, T. A. (2005) Peptide-conjugated quantum dots activate neuronal receptors and initiate downstream signaling of neurite growth. Nano Lett. 5, 603–607.Google Scholar
  140. 140.
    Hoshino, A., Manabe, N., Fujioka, K., Hanada, S., Yasuhara, M., Kondo, A., Yamamoto, K. (2008) GFP expression by intracellular gene delivery of GFP-coding fragments using nanocrystal quantum dots. Nanotechnology. 19, 495102.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Nikodem Tomczak
    • 1
    Email author
  • Dominik Jańczewski
    • 1
  • Denis Dorokhin
    • 2
    • 3
  • Ming-Yong Han
    • 1
    • 4
  • G. Julius Vancso
    • 2
    • 3
    • 4
  1. 1.Institute of Materials Research and EngineeringA*STAR (Agency for Science, Technology and Research)SingaporeSingapore
  2. 2.Faculty of Science and Technology, Materials Science and Technology of PolymersUniversity of TwenteEnschedeThe Netherlands
  3. 3.MESA + Institute for NanotechnologyEnschedeThe Netherlands
  4. 4.Division of BioengineeringNational University of SingaporeSingaporeSingapore

Personalised recommendations