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Protein–inorganic hybrid nanoflowers


Flower-shaped inorganic nanocrystals1,2,3 have been used for applications in catalysis4,5 and analytical science6,7, but so far there have been no reports of ‘nanoflowers’ made of organic components8. Here, we report a method for creating hybrid organic–inorganic nanoflowers using copper (II) ions as the inorganic component and various proteins as the organic component. The protein molecules form complexes with the copper ions, and these complexes become nucleation sites for primary crystals of copper phosphate. Interaction between the protein and copper ions then leads to the growth of micrometre-sized particles that have nanoscale features and that are shaped like flower petals. When an enzyme is used as the protein component of the hybrid nanoflower, it exhibits enhanced enzymatic activity and stability compared with the free enzyme. This is attributed to the high surface area and confinement of the enzymes in the nanoflowers.

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Figure 1: Hybrid nanoflowers made from BSA and Cu3(PO4)2·3H2O.
Figure 2: Formation of BSA-incorporated Cu3(PO4)2·3H2O nanoflowers.
Figure 3: SEM images of hybrid nanoflowers.
Figure 4: Detection of epinephrine by laccase nanoflowers.


  1. Song, Y. et al. Controlled synthesis of 2-D and 3-D dendritic platinum nanostructures. J. Am. Chem. Soc. 126, 635–645 (2004).

    Article  CAS  Google Scholar 

  2. Narayanaswamy, A., Xu, H., Pradhan, N., Kim, M. & Peng, X. Formation of nearly monodisperse In2O3 nanodots and oriented-attached nanoflowers: hydrolysis and alcoholysis vs pyrolysis. J. Am. Chem. Soc. 128, 10310–10319 (2006).

    Article  CAS  Google Scholar 

  3. Sun, Z. et al. Rational design of 3D dendritic TiO2 nanostructures with favorable architectures. J. Am. Chem. Soc. 133, 19314–19317 (2011).

    Article  CAS  Google Scholar 

  4. Lim, B. et al. Pd–Pt bimetallic nanodendrites with high activity for oxygen reduction. Science 324, 1302–1305 (2009).

    Article  CAS  Google Scholar 

  5. Mohanty, A., Garg, N. & Jin, R. A universal approach to the synthesis of noble metal nanodendrites and their catalytic properties. Angew. Chem. Int. Ed. 49, 4962–4966 (2010).

    Article  CAS  Google Scholar 

  6. Xie, J., Zhang, Q., Lee, J. Y. & Wang, D. I. C. The synthesis of SERS-active gold nanoflower tags for in vivo applications. ACS Nano 2, 2473–2480 (2008).

    Article  CAS  Google Scholar 

  7. Jia, W., Su, L. & Lei, Y. Pt nanoflower/polyaniline composite nanofibers based urea biosensor. Biosens. Bioelectron. 30, 158–164 (2011).

    Article  CAS  Google Scholar 

  8. Kharisov, B. I. A review for synthesis of nanoflowers. Recent Pat. Nanotechnol. 2, 190–200 (2008).

    Article  CAS  Google Scholar 

  9. Harford, C. & Sarkar, B. Amino terminal Cu(II) and Ni(II)-binding (ATCUN) motif of proteins and peptides. Acc. Chem. Res. 30, 123–130 (1997).

    Article  CAS  Google Scholar 

  10. Smith, P. K. et al. Measurement of protein using bicinchoninic acid. Anal. Biochem. 150, 76–85 (1985).

    Article  CAS  Google Scholar 

  11. Rulíšek, L. & Vondrášek, J. Coordination geometries of selected transition metal ions (Co2+, Ni2+, Cu2+, Zn2+, Cd2+, and Hg2+) in metalloproteins. J. Inorg. Biochem. 71, 115–127 (1998).

    Article  Google Scholar 

  12. Chandra, N., Brew, K. & Acharya, K. R. Structural evidence for the presence of a secondary calcium binding site in human alpha-lactalbumin. Biochemistry 37, 4767–4772 (1998).

    Article  CAS  Google Scholar 

  13. Piontek, K., Antorini, M. & Choinowski, T. Crystal structure of a laccase from the fungus Trametes versicolor at 1.90-Å resolution containing a full complement of coppers. J. Biol. Chem. 277, 37663–37669 (2002).

    Article  CAS  Google Scholar 

  14. Saito, R., Sato, T., Ikai, A. & Tanaka, N. Structure of bovine carbonic anhydrase II at 1.95 Å resolution. Acta Crystallogr. D 60, 792–795 (2004).

    Article  Google Scholar 

  15. Ericsson, D. J. et al. X-ray structure of Candida antarctica lipase A shows a novel lid structure and a likely mode of interfacial activation. J. Mol. Biol. 376, 109–119 (2008).

    Article  CAS  Google Scholar 

  16. Kudva, Y. C., Sawka, A. M. & Young, W. F. Jr Clinical review 164: the laboratory diagnosis of adrenal pheochromocytoma: the Mayo Clinic experience. J. Clin. Endocrinol. Metab. 88, 4533–4539 (2003).

    Article  CAS  Google Scholar 

  17. Morita, E. & Nakamura, E. Solid-phase extraction of antipyrine dye for spectrophotometric determination of phenolic compounds in water. Anal. Sci. 27, 489–492 (2011).

    Article  CAS  Google Scholar 

  18. Kim, J., Grate, J. W. & Wang, P. Nanobiocatalysis and its potential applications. Trends Biotechnol. 26, 639–646 (2008).

    Article  CAS  Google Scholar 

  19. Ge, J., Lu, D., Liu, Z. X. & Liu, Z. Recent advances in nanostructured biocatalysts. Biochem. Eng. J. 44, 53–59 (2009).

    Article  CAS  Google Scholar 

  20. Luckarift, H. R., Spain, J. C., Naik, R. R. & Stone, M. O. Enzyme immobilization in a biomimetic silica support. Nature Biotechnol. 22, 211–213 (2004).

    Article  CAS  Google Scholar 

  21. Mateo, C. et al. Immobilization of enzymes on heterofunctional epoxy supports. Nature Protoc. 2, 1022–1027 (2007).

    Article  CAS  Google Scholar 

  22. Kim, J. & Grate, J. W. Single-enzyme nanoparticles armored by a nanometer-scale organic/inorganic network. Nano Lett. 3, 1219–1222 (2003).

    Article  CAS  Google Scholar 

  23. Yan, M., Ge, J., Liu, Z. & Ouyang, P. Encapsulation of single enzyme in nanogel with enhanced biocatalytic activity and stability. J. Am. Chem. Soc. 128, 11008–11009 (2006).

    Article  CAS  Google Scholar 

  24. Ge, J. et al. Molecular fundamentals of enzyme nanogels. J. Phys. Chem. B 112, 14319–14324 (2008).

    Article  CAS  Google Scholar 

  25. Ge, J., Lu, D., Wang, J. & Liu, Z. Lipase nanogel catalyzed transesterification in anhydrous dimethyl sulfoxide. Biomacromolecules 10, 1612–1618 (2009).

    Article  CAS  Google Scholar 

  26. Yan, M., Liu, Z. X., Lu, D. & Liu, Z. Fabrication of single carbonic anhydrase nanogel against denaturation and aggregation at high temperature. Biomacromolecules 8, 560–565 (2007).

    Article  CAS  Google Scholar 

  27. Lei, C., Shin, Y., Liu, J. & Ackerman, E. J. Entrapping enzyme in a functionalized nanoporous support. J. Am. Chem. Soc. 124, 11242–11243 (2002).

    Article  CAS  Google Scholar 

  28. Dulay, M. T., Baca, Q. J. & Zare, R. N. Enhanced proteolytic activity of covalently bound enzymes in photopolymerized sol gel. Anal. Chem. 77, 4604–4610 (2005).

    Article  CAS  Google Scholar 

  29. Murugesan, K., Kim, Y-M., Jeon, J-R. & Chang, Y-S. Effect of metal ions on reactive dye decolorization by laccase from Ganoderma lucidum. J. Hazard. Mater. 168, 523–529 (2009).

    Article  CAS  Google Scholar 

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The authors thank J. Brauman and K. Holmberg for helpful discussions and R-L. Jia for helping with acquiring TEM images. All experimental work was performed at Stanford University and was financially supported by the US National Science Foundation (CBET-0827806).

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Authors and Affiliations



J.G., J.L. and R.N.Z. conceived and designed the experiments. J.G. and J.L. performed the experiments. J.G. and R.N.Z. analysed the data and wrote the paper.

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Correspondence to Richard N. Zare.

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The authors declare no competing financial interests.

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Ge, J., Lei, J. & Zare, R. Protein–inorganic hybrid nanoflowers. Nature Nanotech 7, 428–432 (2012).

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