Skip to main content
Log in

Enhanced and tunable fluorescent quantum dots within a single crystal of protein

  • Research Article
  • Published:
Nano Research Aims and scope Submit manuscript

Abstract

The design and synthesis of bio-nano hybrid materials can not only provide new materials with novel properties, but also advance our fundamental understanding of interactions between biomolecules and their abiotic counterparts. Here, we report a new approach to achieving such a goal by growing CdS quantum dots (QDs) within single crystals of lysozyme protein. This bio-nano hybrid emitted much stronger red fluorescence than its counterpart without the crystal, and such fluorescence properties could be either enhanced or suppressed by the addition of Ag(I) or Hg(II), respectively. The three-dimensional incorporation of CdS QDs within the lysozyme crystals was revealed by scanning transmission electron microscopy with electron tomography. More importantly, since our approach did not disrupt the crystalline nature of the lysozyme crystals, the metal and protein interactions were able to be studied by X-ray crystallography, thus providing insight into the role of Cd(II) in the CdS QDs formation.

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

Similar content being viewed by others

References

  1. Niemeyer, C. M.; Mirkin, C. A. Nanobiotechnology II: More concepts and applications; WILEY-VCH: Weinheim, 2004.

    Book  Google Scholar 

  2. Xue, X. J.; Wang, F.; Liu, X. G. One-step, room temperature, colorimetric detection of mercury (Hg2+) using DNA/nanoparticle conjugates. J. Am. Chem. Soc. 2008, 130, 3244–3245.

    Article  CAS  Google Scholar 

  3. Suzuki, M.; Abe, M.; Ueno, T.; Abe, S.; Goto, T.; Toda, Y.; Akita, T.; Yamadae, Y.; Watanabe, Y. Preparation and catalytic reaction of Au/Pd bimetallic nanoparticles in Apo-ferritin. Chem. Commun. 2009, 4871–4873.

    Google Scholar 

  4. Ruiz-Hitzky, E.; Darder, M.; Aranda, P.; Ariga, K. Advances in biomimetic and nanostructured biohybrid materials. Adv. Mater. 2010, 22, 323–336.

    Article  CAS  Google Scholar 

  5. Wang, F.; Tan, W. B.; Zhang, Y.; Fan, X. P.; Wang, M. Q. Luminescent nanomaterials for biological labelling. Nanotechnology 2006, 17, R1–R13.

    Article  CAS  Google Scholar 

  6. Yan, J. L.; Estevez, M. C.; Smith, J. E.; Wang, K. M.; He, X. X.; Wang, L.; Tan, W. H. Dye-doped nanoparticles for bioanalysis. Nano Today 2007, 2, 44–50.

    Article  Google Scholar 

  7. Lu, Y.; Liu, J. W. Smart nanomaterials inspired by biology: Dynamic assembly of error-free nanomaterials in response to multiple chemical and biological stimuli. Acc. Chem. Res. 2007, 40, 315–323.

    Article  CAS  Google Scholar 

  8. Wang, Z. D.; Lu, Y. Functional DNA directed assembly of nanomaterials for biosensing. J. Mater. Chem. 2009, 19, 1788–1798.

    Article  CAS  Google Scholar 

  9. Lee, J. H.; Yigit, M. V.; Mazumdar, D.; Lu, Y. Molecular diagnostic and drug delivery agents based on aptamer-nanomaterial conjugates. Adv. Drug Deliv. Rev. 2010, 62, 592–605.

    Article  CAS  Google Scholar 

  10. Xing, H.; Wong, N. Y.; Xiang, Y.; Lu, Y. DNA aptamer functionalized nanomaterials for intracellular analysis, cancer cell imaging and drug delivery. Curr. Opin. Chem. Biol. 2012, 16, 429–435.

    Article  CAS  Google Scholar 

  11. Pal, S.; Sharma, J.; Yan, H.; Liu, Y. Stable silver nanoparticle-DNA conjugates for directed self-assembly of core-satellite silver-gold nanoclusters. Chem. Commun. 2009, 6059–6061.

    Google Scholar 

  12. Choi, S.; Dickson, R. M.; Yu, J. Developing luminescent silver nanodots for biological applications. Chem. Soc. Rev. 2012, 41, 1867–1891.

    Article  CAS  Google Scholar 

  13. Dickerson, M. B.; Sandhage, K. H.; Naik, R. R. Protein- and peptide-directed syntheses of inorganic materials. Chem. Rev. 2008, 108, 4935–4978.

    Article  CAS  Google Scholar 

  14. Sanders, L. K.; Xian, W. J.; Guaqueta, C.; Strohman, M. J.; Vrasich, C. R.; Luijten, E.; Wong, G. C. L. Control of electrostatic interactions between F-actin and genetically modified lysozyme in aqueous media. Proc. Natl. Acad. Sci. U. S. A. 2007, 104, 15994–15999.

    Article  CAS  Google Scholar 

  15. Zhang, M. G.; Smith, A.; Gorski, W. Carbon nanotube-chitosan system for electrochemical sensing based on dehydrogenase enzymes. Anal. Chem. 2004, 76, 5045–5050.

    Article  CAS  Google Scholar 

  16. Lee, Y. J.; Yi, H.; Kim, W. J.; Kang, K.; Yun, D. S.; Strano, M. S.; Ceder, G.; Belcher, A. M. Fabricating genetically engineered high-power lithium-ion batteries using multiple virus genes. Science 2009, 324, 1051–1055.

    CAS  Google Scholar 

  17. Park, T. J.; Lee, S. Y.; Heo, N. S.; Seo, T. S. In vivo synthesis of diverse metal nanoparticles by recombinant Escherichia coli. Angew. Chem. Int. Ed. 2010, 49, 7019–7024.

    Article  CAS  Google Scholar 

  18. Sturzenbaum, S. R.; Hockner, M.; Panneerselvam, A.; Levitt, J.; Bouillard, J. S.; Taniguchi, S.; Dailey, L. A.; Khanbeigi, R. A.; Rosca, E. V.; Thanou, M. et al. Biosynthesis of luminescent quantum dots in an earthworm. Nat. Nanotechnol. 2013, 8, 57–60.

    Article  CAS  Google Scholar 

  19. Bao, H. F.; Lu, Z. S.; Cui, X. Q.; Qiao, Y.; Guo, J.; Anderson, J. M.; Li, C. M. Extracellular microbial synthesis of biocompatible CdTe quantum dots. Acta Biomater. 2010, 6, 3534–3541.

    Article  CAS  Google Scholar 

  20. Liu, J. W.; Lu, Y. A colorimetric lead biosensor using DNAzyme-directed assembly of gold nanoparticles. J. Am. Chem. Soc. 2003, 125, 6642–6643.

    Article  CAS  Google Scholar 

  21. Wei, H.; Wang, Z. D.; Yang, L. M.; Tian, S. L.; Hou, C. J.; Lu, Y. Lysozyme-stabilized gold fluorescent cluster: Synthesis and application as Hg2+ sensor. Analyst 2010, 135, 1406–1410.

    Article  CAS  Google Scholar 

  22. Xing, H.; Wang, Z. D.; Xu, Z. D.; Wong, N. Y.; Xiang, Y.; Liu, G. L. G.; Lu, Y. DNA-directed assembly of asymmetric nanoclusters using Janus nanoparticles. ACS Nano 2012, 6, 802–809.

    Article  CAS  Google Scholar 

  23. Li, L. L.; Zhang, R. B.; Yin, L. L.; Zheng, K. Z.; Qin, W. P.; Selvin, P. R.; Lu, Y. Biomimetic surface engineering of lanthanide-doped upconversion nanoparticles as versatile bioprobes. Angew. Chem. Int. Ed. 2012, 51, 6121–6125.

    Article  CAS  Google Scholar 

  24. Li, L. L.; Yin, Q.; Cheng, J. J.; Lu, Y. Polyvalent mesoporous silica nanoparticle-aptamer bioconjugates target breast cancer cells. Adv. Healthcare Mater. 2012, 1, 567–572.

    Article  CAS  Google Scholar 

  25. Wang, Z. D.; Tang, L. H.; Tan, L. H.; Li, J. H.; Lu, Y. Discovery of the DNA “genetic code” for abiological gold nanoparticle morphologies. Angew. Chem. Int. Ed. 2012, 51, 9078–9082.

    Article  CAS  Google Scholar 

  26. Wu, P. W.; Hwang, K.; Lan, T.; Lu, Y. A DNAzyme-gold nanoparticle probe for uranyl ion in living cells. J. Am. Chem. Soc. 2013, 135, 5254–5257.

    Article  CAS  Google Scholar 

  27. Li, L. L.; Wu, P. W.; Hwang, K.; Lu, Y. An exceptionally simple strategy for DNA-functionalized up-conversion nanoparticles as biocompatible agents for nanoassembly, DNA delivery, and imaging. J. Am. Chem. Soc. 2013, 135, 2411–2414.

    Article  CAS  Google Scholar 

  28. Ueno, T.; Abe, S.; Yokoi, N.; Watanabe, Y. Coordination design of artificial metalloproteins utilizing protein vacant space. Coord. Chem. Rev. 2007, 251, 2717–2731.

    Article  CAS  Google Scholar 

  29. Xie, J. P.; Zheng, Y. G.; Ying, J. Y. Protein-directed synthesis of highly fluorescent gold nanoclusters. J. Am. Chem. Soc. 2009, 131, 888–889.

    Article  CAS  Google Scholar 

  30. Medalsy, I.; Dgany, O.; Sowwan, M.; Cohen, H.; Yukashevska, A.; Wolf, S. G.; Wolf, A.; Koster, A.; Almog, O.; Marton, I. et al. SP1 protein-based nanostructures and arrays. Nano Lett. 2008, 8, 473–477.

    Article  CAS  Google Scholar 

  31. Dani, R. K.; Kang, M.; Kalita, M.; Smith, P. E.; Bossmann, S. H.; Chikan, V. MspA porin-gold nanoparticle assemblies: Enhanced binding through a controlled cysteine mutation. Nano Lett. 2008, 8, 1229–1236.

    Article  CAS  Google Scholar 

  32. Guo, C. L.; Irudayaraj, J. Fluorescent Ag clusters via a protein-directed approach as a Hg(II) ion sensor. Anal. Chem. 2011, 83, 2883–2889.

    Article  CAS  Google Scholar 

  33. Chaudhari, K.; Xavier, P. L.; Pradeep, T. Understanding the evolution of luminescent gold quantum clusters in protein templates. ACS Nano 2011, 5, 8816–8827.

    Article  CAS  Google Scholar 

  34. Ge, J.; Lei, J. D.; Zare, R. N. Protein-inorganic hybrid nanoflowers. Nat. Nanotechnol. 2012, 7, 428–432.

    Article  CAS  Google Scholar 

  35. Wang, Y. C.; Wang, Y.; Zhou, F. B.; Kim, P.; Xia, Y. N. Protein-protected Au clusters as a new class of nanoscale biosensor for label-free fluorescence detection of proteases. Small 2012, 8, 3769–3773.

    Article  CAS  Google Scholar 

  36. Colombo, M.; Mazzucchelli, S.; Collico, V.; Avvakumova, S.; Pandolfi, L.; Corsi, F.; Porta, F.; Prosperi, D. Protein-assisted one-pot synthesis and biofunctionalization of spherical gold nanoparticles for selective targeting of cancer cells. Angew. Chem. Int. Ed. 2012, 51, 9272–9275.

    Article  CAS  Google Scholar 

  37. Chen, T. H.; Tseng, W. L. (Lysozyme type VI)-stabilized Au8 clusters: Synthesis mechanism and application for sensing of glutathione in a single drop of blood. Small 2012, 8, 1912–1919.

    Article  CAS  Google Scholar 

  38. Meldrum, F. C.; Wade, V. J.; Nimmo, D. L.; Heywood, B. R.; Mann, S. Synthesis of inorganic nanophase materials in supramolecular protein cages. Nature 1991, 349, 684–687.

    Article  CAS  Google Scholar 

  39. Uchida, M.; Klem, M. T.; Allen, M.; Suci, P.; Flenniken, M.; Gillitzer, E.; Varpness, Z.; Liepold, L. O.; Young, M.; Douglas, T. Biological containers: Protein cages as multifunctional nanoplatforms. Adv. Mater. 2007, 19, 1025–1042.

    Article  CAS  Google Scholar 

  40. Butts, C. A.; Swift, J.; Kang, S. G.; Di Costanzo, L.; Christianson, D. W.; Saven, J. G.; Dmochowski, I. J. Directing noble metal ion chemistry within a designed ferritin protein. Biochemistry 2008, 47, 12729–12739.

    Article  CAS  Google Scholar 

  41. Margolin, A. L.; Navia, M. A. Protein crystals as novel catalytic materials. Angew. Chem. Int. Ed. 2001, 40, 2204–2222.

    Article  CAS  Google Scholar 

  42. Sanghamitraa, N. J. M.; Ueno, T. Expanding coordination chemistry from protein to protein assembly. Chem. Commun. 2013, 49, 4114–4126.

    Article  Google Scholar 

  43. Falkner, J. C.; Turner, M. E.; Bosworth, J. K.; Trentler, T. J.; Johnson, J. E.; Lin, T. W.; Colvin, V. L. Virus crystals as nanocomposite scaffolds. J. Am. Chem. Soc. 2005, 127, 5274–5275.

    Article  CAS  Google Scholar 

  44. Guli, M.; Lambert, E. M.; Li, M.; Mann, S. Template-directed synthesis of nanoplasmonic arrays by intracrystalline metalization of cross-linked lysozyme crystals. Angew. Chem. Int. Ed. 2010, 49, 520–523.

    Article  CAS  Google Scholar 

  45. Ueno, T.; Abe, S.; Koshiyama, T.; Ohki, T.; Hikage, T.; Watanabe, Y. Elucidation of metal-ion accumulation induced by hydrogen bonds on protein surfaces by using porous lysozyme crystals containing Rh-III ions as the model surfaces. Chem. Eur. J. 2010, 16, 2730–2740.

    Article  CAS  Google Scholar 

  46. Wei, H.; Wang, Z. D.; Zhang, J.; House, S.; Gao, Y. G.; Yang, L. M.; Robinson, H.; Tan, L. H.; Xing, H.; Hou, C. J. et al. Time-dependent, protein-directed growth of gold nanoparticles within a single crystal of lysozyme. Nat. Nanotechnol. 2011, 6, 93–97.

    Article  CAS  Google Scholar 

  47. Vekilov, P. G. Gold nanoparticles grown in a crystal. Nat. Nanotechnol. 2011, 6, 82–83.

    Article  CAS  Google Scholar 

  48. Liu, C. L.; Wu, H. T.; Hsiao, Y. H.; Lai, C. W.; Shih, C. W.; Peng, Y. K.; Tang, K. C.; Chang, H. W.; Chien, Y. C.; Hsiao, J. K. et al. Insulin-directed synthesis of fluorescent gold nanoclusters: Preservation of insulin bioactivity and versatility in cell imaging. Angew. Chem. Int. Ed. 2011, 50, 7056–7060.

    Article  CAS  Google Scholar 

  49. Wei, H.; Lu, Y. Catalysis of gold nanoparticles within lysozyme single crystals. Chem. Asian J. 2012, 7, 680–683.

    Article  CAS  Google Scholar 

  50. Abe, S.; Tsujimoto, M.; Yoneda, K.; Ohba, M.; Hikage, T.; Takano, M.; Kitagawa, S.; Ueno, T. Porous protein crystals as reaction vessels for controlling magnetic properties of nanoparticles. Small 2012, 8, 1314–1319.

    Article  CAS  Google Scholar 

  51. Steigerwald, M. L.; Brus, L. E. Semiconductor crystallites: A class of large molecules. Acc. Chem. Res. 1990, 23, 183–188.

    Article  CAS  Google Scholar 

  52. Chan, W. C. W.; Nie, S. M. Quantum dot bioconjugates for ultrasensitive nonisotopic detection. Science 1998, 281, 2016–2018.

    Article  CAS  Google Scholar 

  53. Bruchez, M.; Moronne, M.; Gin, P.; Weiss, S.; Alivisatos, A. P. Semiconductor nanocrystals as fluorescent biological labels. Science 1998, 281, 2013–2016.

    Article  CAS  Google Scholar 

  54. Bhattacharya, P.; Ghosh, S.; Stiff-Roberts, A. D. Quantum dot opto-electronic devices. Ann. Rev. Mater. Res. 2004, 34, 1–40.

    Article  CAS  Google Scholar 

  55. Gao, X. H.; Cui, Y. Y.; Levenson, R. M.; Chung, L. W. K.; Nie, S. M. In vivo cancer targeting and imaging with semiconductor quantum dots. Nat. Biotechnol. 2004, 22, 969–976.

    Article  CAS  Google Scholar 

  56. Sargent, E. H. Colloidal quantum dot solar cells. Nat. Photonics 2012, 6, 133–135.

    Article  CAS  Google Scholar 

  57. Regulacio, M. D.; Han, M. Y. Composition-tunable alloyed semiconductor nanocrystals. Acc. Chem. Res. 2010, 43, 621–630.

    Article  CAS  Google Scholar 

  58. Peng, X. G.; Manna, L.; Yang, W. D.; Wickham, J.; Scher, E.; Kadavanich, A.; Alivisatos, A. P. Shape control of CdSe nanocrystals. Nature 2000, 404, 59–61.

    Article  CAS  Google Scholar 

  59. Li, Z.; Qin, H. Y.; Guzun, D.; Benamara, M.; Salamo, G.; Peng, X. G. Uniform thickness and colloidal-stable CdS quantum disks with tunable thickness: Synthesis and properties. Nano Res. 2012, 5, 337–351.

    Article  CAS  Google Scholar 

  60. Li, F.; Zhang, Z. P.; Peng, J.; Cui, Z. Q.; Pang, D. W.; Li, K.; Wei, H. P.; Zhou, Y. F.; Wen, J. K.; Zhang, X. E. Imaging viral behavior in mammalian cells with self-assembled capsid-quantum-dot hybrid particles. Small 2009, 5, 718–726.

    Article  CAS  Google Scholar 

  61. Hu, M.; Yan, J.; He, Y.; Lu, H. T.; Weng, L. X.; Song, S. P.; Fan, C. H.; Wang, L. H. Ultrasensitive, multiplexed detection of cancer biomarkers directly in serum by using a quantum dot-based microfluidic protein chip. ACS Nano 2010, 4, 488–494.

    Article  CAS  Google Scholar 

  62. Xiao, Q.; Huang, S.; Qi, Z. D.; Zhou, B.; He, Z. K.; Liu, Y. Conformation, thermodynamics and stoichiometry of HSA adsorbed to colloidal CdSe/ZnS quantum dots. BBA-Proteins Proteomics 2008, 1784, 1020–1027.

    Article  CAS  Google Scholar 

  63. Chen, L. D.; Liu, J.; Yu, X. F.; He, M.; Pei, X. F.; Tang, Z. Y.; Wang, Q. Q.; Pang, D. W.; Li, Y. The biocompatibility of quantum dot probes used for the targeted imaging of hepatocellular carcinoma metastasis. Biomaterials 2008, 29, 4170–4176.

    Article  CAS  Google Scholar 

  64. Qu, Y.; Li, W.; Zhou, Y. L.; Liu, X. F.; Zhang, L. L.; Wang, L. M.; Li, Y. F.; Iida, A.; Tang, Z. Y.; Zhao, Y. L. et al. Full assessment of fate and physiological behavior of quantum dots utilizing caenorhabditis elegans as a model organism. Nano Lett. 2011, 11, 3174–3183.

    Article  CAS  Google Scholar 

  65. Kang, Z. H.; Liu, Y.; Tsang, C. H. A.; Ma, D. D. D.; Fan, X.; Wong, N. B.; Lee, S. T. Water-soluble silicon quantum dots with wavelength-tunable photoluminescence. Adv. Mater. 2009, 21, 661–664.

    Article  CAS  Google Scholar 

  66. Liu, J. W.; Lee, J. H.; Lu, Y. Quantum dot encoding of aptamer-linked nanostructures for one-pot simultaneous detection of multiple analytes. Anal. Chem. 2007, 79, 4120–4125.

    Article  CAS  Google Scholar 

  67. Resch, U.; Eychmuller, A.; Haase, M.; Weller, H. Absorption and fluorescence behavior of redispersible Cds colloids in various organic-solvents. Langmuir 1992, 8, 2215–2218.

    Article  CAS  Google Scholar 

  68. Dameron, C. T.; Reese, R. N.; Mehra, R. K.; Kortan, A. R.; Carroll, P. J.; Steigerwald, M. L.; Brus, L. E.; Winge, D. R. Biosynthesis of cadmium-sulfide quantum semiconductor crystallites. Nature 1989, 338, 596–597.

    Article  CAS  Google Scholar 

  69. Wong, K. K. W.; Mann, S. Biomimetic synthesis of cadmium sulfide-ferritin nanocomposites. Adv. Mater. 1996, 8, 928–932.

    Article  CAS  Google Scholar 

  70. Naito, M.; Iwahori, K.; Miura, A.; Yamane, M.; Yamashita, I. Circularly polarized luminescent CdS quantum dots prepared in a protein nanocage. Angew. Chem. Int. Ed. 2010, 49, 7006–7009.

    Article  CAS  Google Scholar 

  71. Zheng, Y. G.; Yang, Z. C.; Ying, J. Y. Aqueous synthesis of glutathione-capped ZnSe and Zn1−x CdxSe alloyed quantum dots. Adv. Mater. 2007, 19, 1475–1479.

    Article  CAS  Google Scholar 

  72. Arslan, I.; Yates, T. J. V.; Browning, N. D.; Midgley, P. A. Embedded nanostructures revealed in three dimensions. Science 2005, 309, 2195–2198.

    Article  CAS  Google Scholar 

  73. Li, H. Y.; Xin, H. L.; Muller, D. A.; Estroff, L. A. Visualizing the 3D internal structure of calcite single crystals grown in agarose hydrogels. Science 2009, 326, 1244–1247.

    Article  CAS  Google Scholar 

  74. Chen, J. L.; Zhu, C. Q. Functionalized cadmium sulfide quantum dots as fluorescence probe for silver ion determination. Anal. Chim. Acta 2005, 546, 147–153.

    Article  CAS  Google Scholar 

  75. Han, B. Y.; Yuan, J. P.; Wang, E. K. Sensitive and selective sensor for biothiols in the cell based on the recovered fluorescence of the CdTe quantum dots-Hg(II) system. Anal. Chem. 2009, 81, 5569–5573.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Jianmin Zuo, Ian M. Robertson or Yi Lu.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wei, H., House, S., Wu, J. et al. Enhanced and tunable fluorescent quantum dots within a single crystal of protein. Nano Res. 6, 627–634 (2013). https://doi.org/10.1007/s12274-013-0348-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12274-013-0348-0

Keywords

Navigation