Nano Research

, Volume 1, Issue 2, pp 99–115 | Cite as

Bioconjugated silica nanoparticles: Development and applications

Open Access
Review Article

Abstract

Advanced bioanalysis, including accurate quantitation, has driven the need to understand biology and medicine at the molecular level. Bioconjugated silica nanoparticles have the potential to address this emerging challenge. Particularly intriguing diagnostic and therapeutic applications in cancer and infectious disease as well as uses in gene and drug delivery, have also been found for silica nanoparticles. In this review, we describe the synthesis, bioconjugation, and applications of silica nanoparticles in different bioanalysis formats, such as selective tagging, barcoding, and separation of a wide range of biomedically important targets. Overall, we envisage that further development of these nanoparticles will provide a variety of advanced tools for molecular biology, genomics, proteomics and medicine.

Keywords

Nanoscience nanotechnology silica nanoparticles bioanalysis biomedicine 

Supplementary material

12274_2008_8018_MOESM1_ESM.mov (1 mb)
Supplementary material, approximately 1.02 MB.
12274_2008_8018_MOESM1_ESM.pdf (2.8 mb)
Supplementary material, approximately 2.75 MB.

References

  1. [1]
    Niemeyer, C. M. Nanoparticles, proteins, and nucleic acids: Biotechnology meets materials science. Angew. Chem. Int. Ed. 2001, 40, 4128–4158.CrossRefGoogle Scholar
  2. [2]
    Gao, X. H; Nie, S. M. Molecular profiling of single cells and tissue specimens with quantum dots. Trends Biotechnol. 2003, 21, 371–373.CrossRefGoogle Scholar
  3. [3]
    Nicewarner-Pena, S. R.; Freeman, R. G.; Reiss, B. D. Submicrometer metallic barcodes. Science 2001, 294, 137–141.CrossRefGoogle Scholar
  4. [4]
    Rosi, N. L.; Giljohann, D. A.; Thaxton, C. S.; Lytton-Jean, A. K. R.; Han, M. S.; Mirkin, C. A. Oligonucleotidemodified gold nanoparticles for intracellular gene regulation. Science 2006, 312, 1027–1030.CrossRefGoogle Scholar
  5. [5]
    Medintz, I. L.; Uyeda, H. T.; Goldman, E. R.; Mattoussi, H. Quantum dot bioconjugates for imaging, labeling and sensing. Nat. Mater. 2005, 4, 435–446.CrossRefGoogle Scholar
  6. [6]
    Smith, A. M.; Dave, S. V.; Nie, S. M.; True, L.; Gao, X. H. Multicolor quantum dots for molecular diagnostics of cancer. Expert Rev. Mol. Diagn. 2006, 6, 231–244.CrossRefGoogle Scholar
  7. [7]
    Atanasijevic, T.; Shusteff, M.; Fam, P.; Jasanoff, A. Calciumsensitive MRI contrast agents based on superparamagnetic iron oxide nanoparticles and calmodulin. P. Natl. Acad. Sci. USA 2006, 103, 14707–14712.CrossRefGoogle Scholar
  8. [8]
    Salata, O. V. Applications of nanoparticles in biology and medicine. J. Nanobiotechnol. 2004, 2, 3–8.CrossRefGoogle Scholar
  9. [9]
    Stroh, M.; Zimmer, J. P.; Duda, D. G.; Levchenko, T. S.; Cohen, K. S.; Brown, E. B.; Scadden, D. T.; Torchilin, V. P.; Bawendi, M. G.; Fukumura, D.; Jain, R. K. Quantum dots spectrally distinguish multiple species within the tumor milieu in vivo. Nat. Med. 2005, 11, 678–682.CrossRefGoogle Scholar
  10. [10]
    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. Quantum dots for live cells, in vivo imaging, and diagnostics. Science 2005, 307, 538–544.CrossRefGoogle Scholar
  11. [11]
    Mirkin, C. A.; Letsinger, R. L.; Mucic, R. C.; Storhoff, J. J. A DNA-based method for rationally assembling nanoparticles into macroscopic materials. Nature 1996, 382, 607–609.CrossRefGoogle Scholar
  12. [12]
    Daniel, M. C.; Astruc, D. Gold nanoparticles: Assembly, supramolecular chemistry, quantum-size-related properties, and applications toward biology, catalysis, and nanotechnology. Chem. Rev. 2004, 104, 293–346.CrossRefGoogle Scholar
  13. [13]
    Nichkova, M.; Dosev, D.; Gee, S. J.; Hammock, B. D.; Kennedy, I. M. Microarray immunoassay for phenoxybenzoic acid using polymer encapsulated Eu: Gd2O3 nanoparticles as fluorescent labels. Anal. Chem. 2005, 77, 6864–6873.CrossRefGoogle Scholar
  14. [14]
    Chen, Y.; Chi, Y.; Wen, H.; Lu, Z. Sensitized luminescent terbium nanoparticles: preparation and time-resolved fluorescence assay for DNA. Anal. Chem. 2007, 79, 960–965.CrossRefGoogle Scholar
  15. [15]
    Tan, W. H.; Wang, K. M.; He, X.; Zhao, X. J.; Drake, T.; Wang, L.; Bagwe, R. P. Bionanotechnology based on silica nanoparticles. Med. Res. Rev. 2004, 24, 621–638.CrossRefGoogle Scholar
  16. [16]
    Wang, L.; Wang, K. M.; Swadeshmukul, S.; Zhao, X. J.; Hilliard, L. R.; Smith, J.; Tan, W. H. Watching silica nanoparticles glow in the biological world. Anal. Chem. 2006, 78, 646A–654A.CrossRefGoogle Scholar
  17. [17]
    Yao, G.; Wang, L.; Wu, Y.; Smith, J.; Xu, J.; Zhao, W. Lee, E.; Tan, W. H. FloDots: luminescent nanoparticles. Anal. Bioanal. Chem. 2006, 385, 518–524.CrossRefGoogle Scholar
  18. [18]
    Trewyn, B. G.; Giri, S.; Slowing, I. I.; Lin, V. S. Mesoporous silica nanoparticle based controlled release, drug delivery, and biosensor systems. Chem. Commun. 2007, 3236–3245.Google Scholar
  19. [19]
    Ow, H.; Larson, D. R.; Srivastava, M.; Baird, B. A.; Webb, W. W.; Wiesner, U. Bright and stable core-shell fluorescent silica nanoparticles. Nano Lett. 2005, 5, 113–117.CrossRefGoogle Scholar
  20. [20]
    Ye, Z. Q.; Tan, M. Q.; Wang, G. L.; Yuan, J. L. Novel fluorescent europium chelate-doped silica nanoparticles: preparation, characterization and time-resolved fluorometric application. J. Mater. Chem. 2004, 14, 851–856.CrossRefGoogle Scholar
  21. [21]
    Turney, K.; Drake, T. J.; Smith, J. E.; Tan, W. H.; Harrison, W. W. Functionalized nanoparticles for liquid atmospheric pressure matrix-assisted laser desorption/ionization peptide analysis. Rapid Commun. Mass Spectrom. 2004, 18, 2367–2374.CrossRefGoogle Scholar
  22. [22]
    Hergt, R.; Dutz, S.; Müller, R.; Zeisberger, M. Magnetic particle hyperthermia: nanoparticle magnetism and materials development for cancer therapy. J. Phys.: Condens. Matter 2006, 18, S2919–S2934.CrossRefGoogle Scholar
  23. [23]
    Barbé, C.; Bartlett, J.; Kong, L.; Finnie, K.; Lin, H. Q.; Larkin, M.; Calleja, S.; Bush, A.; Calleja, G. Silica particles: A novel drug-delivery system. Adv. Mater. 2004, 16, 1959–1966.CrossRefGoogle Scholar
  24. [24]
    Wu, J.; Ye, Z. Q.; Wang, G. L.; Yuan, J. L. Multifunctional nanoparticles possessing magnetic, long-lived fluorescence and bio-affinity properties for time-resolved fluorescence cell imaging. Talanta 2007, 72, 1693–1697.CrossRefGoogle Scholar
  25. [25]
    Wu, C. L.; Hong, J. Q.; Guo, X. Q.; Huang, C. B.; Lai, J. P.; Zheng, J. S.; Chen, J. B.; Mu, X.; Zhao, Y. B. Fluorescent Core-shell silica nanoparticles as tunable precursors: Towards encoding and multifunctional nano-probes. Chem. Commun. 2008, 750–752.Google Scholar
  26. [26]
    Yamauchi, H.; Ishikawa, T.; Kondo, S. Surface characterization of ultramicro spherical particles of silica prepared by w/o microemulsion method. Colloids Surf. 1989, 37, 71–80.CrossRefGoogle Scholar
  27. [27]
    Osseo-Asare, K.; Arriagada, F. J. Preparation of SiO2 nanoparticles in a non-ionic reverse micellar system. Colloids Surf. 1990, 50, 321–339.CrossRefGoogle Scholar
  28. [28]
    Lindberg, R.; Sjöblom, J.; Sundholm, G. Preparation of silica particles utilizing the sol-gel and emulsion-gel processes. Colloids Surf. 1995, 99, 79–88.CrossRefGoogle Scholar
  29. [29]
    Santra, S.; Tapec, R.; Theodoropoulou, N.; Dobson, J.; Hebard, A.; Tan, W. H. Synthesis and characterization of silica-coated iron oxide nanoparticles in microemulsion: the effect of nonionic surfactants. Langmuir 2001, 17, 2900–2906.CrossRefGoogle Scholar
  30. [30]
    Santra, S.; Wang, K. M.; Tapec, R.; Tan, W. H. Development of novel dye-doped silica nanoparticles for biomarker application. J. Biomed. Opt. 2001, 6, 160–166.CrossRefGoogle Scholar
  31. [31]
    Santra, S.; Zhang, P.; Wang, K. M.; Tapec, R.; Tan, W. H. Conjugation of biomolecules with luminophore-doped silica nanoparticles for photostable biomarkers. Anal. Chem. 2001, 73, 4988–4993.CrossRefGoogle Scholar
  32. [32]
    Qhobosheane, M.; Santra, S.; Zhang, P.; Tan, W. H. Biochemically functionalized silica nanoparticles. Analyst 2001, 126, 1274–1278.CrossRefGoogle Scholar
  33. [33]
    Wang, L.; Tan, W. H. Multicolor FRET silica nanoparticles by single wavelength excitation. Nano Lett. 2006, 6, 84–88.CrossRefGoogle Scholar
  34. [34]
    Tapec, R.; Zhao, X. J.; Tan, W. H. Development of organic dye-doped silica nanoparticles for bioanalysis and biosensors. J. Nanosci. Nanotechnol. 2002, 2, 405–409.CrossRefGoogle Scholar
  35. [35]
    Zhao, X. J.; Hilliard, L. R.; Mechery, S. J.; Wang, Y.; Bagwe, R. P.; Jin, S.; Tan, W. H. A rapid bioassay for single bacterial cell quantitation using bioconjugated nanoparticles. P. Natl. Acad. Sci. USA 2004, 101, 15027–15032.CrossRefGoogle Scholar
  36. [36]
    Schmidt, J.; Guesdon, C.; Schomäcker, R. Reaction engineering aspects of the preparation of nanocrystalline particles. J. Nanopart. Res. 1999, 1, 267–276.CrossRefGoogle Scholar
  37. [37]
    Stöber, W.; Fink, A.; Bohn, E. Controlled growth of monodisperse silica spheres in micron size range. J. Colloid Interface Sci. 1968, 26, 62–69.CrossRefGoogle Scholar
  38. [38]
    van Blaaderen, A.; Imhof, A.; Hage, W.; Vrij, A. Threedimensional imaging of submicrometer colloidal particles in concentrated suspensions using confocal scanning laser microscopy. Langmuir 1992, 8, 1514–1517.CrossRefGoogle Scholar
  39. [39]
    van Blaaderen, A.; Vrij, A. Synthesis and characterization of colloidal dispersions of fluorescent, monodisperse silica spheres. Langmuir 1992, 8, 2921–2931.CrossRefGoogle Scholar
  40. [40]
    Verhaegh, N. A. M.; van Blaaderen, A. Dispersions of rhodamine-labeled silica spheres: Synthesis, characterization, and fluorescence confocal scanning microscopy. Langmuir 1994, 10, 1427–1438.CrossRefGoogle Scholar
  41. [41]
    Nyffenegger, R.; Quellet, C.; Ricka, J. Synthesis of fluorescent monodisperse, colloidal silica particles. J. Colloid Interface Sci. 1993, 159, 150–157.CrossRefGoogle Scholar
  42. [42]
    Gerion, D.; Pinaud, F.; Williams, S. C.; Parak, W. J.; Zanchet, D.; Weiss, S.; Alivisatos, A. P. Synthesis and properties of biocompatible water-soluble silica-coated CdSe/ZnS semiconductor quantum dots. J. Phys. Chem. B 2001, 105, 8861–8871.CrossRefGoogle Scholar
  43. [43]
    Zhao, X. J.; Tapec-Dytioco, R.; Wang, K. M.; Tan, W. H. Collection of trace amounts of DNA/mRNA molecules using genomagnetic nanocapturers. Anal. Chem. 2003, 75, 3476–3483.CrossRefGoogle Scholar
  44. [44]
    Giri, S.; Trewyn, B. G.; Lin, V. S. Mesoporous silica nanomaterial-based biotechnological and biomedical. Nanomedicine 2007, 2, 99–111.CrossRefGoogle Scholar
  45. [45]
    Lim, M. H.; Blanford, C. F.; Stein, A. Synthesis of ordered microporous silicates with organosulfur surface groups and their applications as solid acid catalysts. Chem. Mater. 1998, 10, 467–470.CrossRefGoogle Scholar
  46. [46]
    Voss, R.; Brook, M. A.; Thompson, J.; Chen, Y.; Pelton, R. H.; Brennan, J. D. Non-destructive horseradish peroxidase immobilization in porous silica nanoparticles. J. Mater. Chem. 2007, 17, 4854–4863.CrossRefGoogle Scholar
  47. [47]
    Santra, S.; Yang, H.; Dutta, D.; Stanley, J. T.; Holloway, P. H.; Tan, W. H.; Moudgil, B. M.; Mericle, R. A. TAT conjugated FITC doped silica nanoparticles for bioimaging applications. Chem. Commun. 2004, 2810–2811.Google Scholar
  48. [48]
    Wang, L.; Lofton, C.; Popp, M.; Tan, W. H. Using luminescent nanoparticles as staining probes for Affymetrix GeneChips. Bioconjugate Chem. 2007, 18, 610–613.CrossRefGoogle Scholar
  49. [49]
    Hermanson, G. T. Bioconjugate Techniques; Academic Press: San Diego, 1996.Google Scholar
  50. [50]
    Roy, I.; Ohulchanskyy, T. Y.; Bharali, D. J.; Pudavar, H. E.; Mistretta, R. A.; Kaur, N.; Prasad, P. N. Optical tracking of organically modified silica nanoparticles as DNA carriers: A nonviral, nanomedicine approach for gene delivery. P. Natl. Acad. Sci. USA 2005, 102, 279–284.CrossRefGoogle Scholar
  51. [51]
    Zhu, S. G.; Xiang, J. J.; Li, X. L.; Shen, S. R.; Lu, H. B.; Zhou, J.; Xiong, W.; Zhang, B. C.; Nie, X. M.; Zhou, M; Tang, K; Li, G. Y. Poly(L-lysine)-modified silica nanoparticles for the delivery of antisense oligonucleotides. Biotechnol. Appl. Bioc. 2004, 39, 179–187.CrossRefGoogle Scholar
  52. [52]
    van Blaaderen, A.; Vrij, A. Synthesis and characterization of monodisperse colloidal organo-silica spheres. J. Colloid Interface Sci. 1993, 156, 1–18.CrossRefGoogle Scholar
  53. [53]
    Bagwe, R. P.; Yang, C.; Hilliard, L.; Tan, W. H. Optimization of dye-doped silica nanoparticles prepared using reverse microemulsion method. Langmuir 2004, 20, 8336–8342.CrossRefGoogle Scholar
  54. [54]
    Zhao, X. J.; Bagwe, R. P.; Tan, W. H. Development of organic-dye-doped silica nanoparticles in reverse microemulsion. Adv. Mater. 2004, 16, 173–176.CrossRefGoogle Scholar
  55. [55]
    Wang, L.; O’ Donoghue, M.; Tan, W. H. Nanoparticles for multiplex diagnostics and imaging. Nanomedicine 2006, 1, 413–426.CrossRefGoogle Scholar
  56. [56]
    Choi, J.; Burns, A. A.; Williams, R. M.; Zhou, Z.; Flesken-Nikitin, A.; Zipfel, W. R.; Wiesner, U.; Nikitin, A. Y. Core-shell silica nanoparticles as fluorescent labels for nanomedicine. J. Biomed. Opt. 2007, 12, 064007.Google Scholar
  57. [57]
    Ow, H.; Larson, D. R.; Srivastava, M.; Baird, B. A.; Webb, W. W.; Wiesner, U. Bright and stable core-shell fluorescent silica nanoparticles. Nano Lett. 2005, 5, 113–117.CrossRefGoogle Scholar
  58. [58]
    He, X. X.; Duan, J. H.; Wang, K. M.; Tan, W. H.; Lin, X.; He, C. M. A novel fluorescent label based on organic dye-doped silica nanoparticles for HepG liver cancer cell recognition. J. Nanosci. Nanotechno. 2004, 4, 585–589.CrossRefGoogle Scholar
  59. [59]
    Santra, S.; Liesenfeld, B.; Dutta, D.; Chatel, D.; Batich, C. D.; Tan, W. H.; Moudgil, B. M.; Mericle, R. A. Folate conjugated fluorescent silica nanoparticles for labeling neoplastic cells. J. Nanosci. Nanotechnol. 2005, 5, 899–904.CrossRefGoogle Scholar
  60. [60]
    Ellington, A. D.; Szostak, J. W. In vitro selection of RNA molecules that bind specific ligands. Nature 1990, 346, 818–822.CrossRefGoogle Scholar
  61. [61]
    Herr, J. K.; Smith, J. E.; Medley, C. D.; Shangguan, D. H.; Tan, W. H. Aptamer-conjugated nanoparticles for selective collection and detection of cancer cells. Anal. Chem. 2006, 78, 2918–2924.CrossRefGoogle Scholar
  62. [62]
    Smith, J. E.; Medley, C. D.; Tang, Z. W.; Shangguan, D. H.; Lofton, C.; Tan, W. H. Aptamer-conjugated nanoparticles for the collection and detection of multiple cancer cells. Anal. Chem. 2007, 79, 3075–3082.CrossRefGoogle Scholar
  63. [63]
    Mechery, S. J.; Zhao, X. J.; Wang, L.; Hilliard, L. R.; Munteanu, A.; Tan, W. H. Using bioconjugated nanoparticles to monitor E. coli in a flow channel. Chem. Asian J. 2006, 1, 384–390.CrossRefGoogle Scholar
  64. [64]
    Hardiman, G. Microarray technologies—2003 An overview. Pharmacogenomics 2003, 4, 251–256.CrossRefGoogle Scholar
  65. [65]
    Zhao, X. J.; Tapec-Dytioco, R.; Tan, W. H. Ultrasensitive DNA detection using highly fluorescent bioconjugated nanoparticles. J. Am. Chem. Soc. 2003, 125, 11474–11475.CrossRefGoogle Scholar
  66. [66]
    Zhou, X.; Zhou, J. Improving the signal sensitivity and photostability of DNA hybridizations on microarrays by using dye-doped core-shell silica nanoparticles. Anal. Chem. 2004, 76, 5302–5312.CrossRefGoogle Scholar
  67. [67]
    Wang, L.; Yang, C. Y.; Tan, W. H. Dual-luminophoredoped silica nanoparticles for multiplexed signaling. Nano Lett. 2005, 5, 37–43.CrossRefGoogle Scholar
  68. [68]
    Wang, L.; Zhao, W.; O’ Donoghue, M.; Tan, W. H. Fluorescent nanoparticles for multiplexed bacteria monitoring. Bioconjugate Chem. 2007, 18, 297–301.CrossRefGoogle Scholar
  69. [69]
    Tartaj, P.; Morales, M. P.; Gonzalez-Carreno, T.; Veintemillas-Verdaguer, S.; Sernam, C. J. Advances in magnetic nanoparticles for biotechnology applications. J. Magn. Magn. Mater. 2005, 290–291, 28–34.Google Scholar
  70. [70]
    Tyagi, S.; Kramer, F. R. Molecular beacons: Probes that fluoresce upon hybridization, Nat. Biotechnol. 1996, 14, 303–308.CrossRefGoogle Scholar
  71. [71]
    Tan, W. H.; Fang, X. H.; Li, J. W.; Liu, X. J. Molecular beacons: A novel DNA probe for nucleic acid and protein studies. Chem.—Eur. J. 2000, 6, 1107–1111.CrossRefGoogle Scholar
  72. [72]
    Ravi Kumar, M. N. V.; Sameti, M.; Mohapatra, S. S.; Kong, X.; Lockey, R. F.; Bakowsky, U.; Lindenblatt, G.; Schmidt, H.; Lehr, C. M. Cationic silica nanoparticles as gene carriers: Synthesis, characterization and transfection efficiency in vitro & in vivo. J. Nanosci. Nanotechnol. 2004, 4, 876–881.CrossRefGoogle Scholar
  73. [73]
    Roy, I.; Ohulchanskyy, T. Y.; Pudavar, H. E.; Bergey, E. J.; Oseroff, A. R.; Morgan, J.; Dougherty, T. J.; Prasad, P. N. Ceramic-based nanoparticles entrapping water-insoluble photosensitizing anticancer drugs: A novel drug-carrier system for photodynamic therapy. J. Am. Chem. Soc. 2003, 125, 7860–7865.CrossRefGoogle Scholar
  74. [74]
    Mary Ann Liebert, Inc. Assessment of adenoviral vector safety and toxicity: report of the National Institutes of Health Recombinant DNA Advisory Committee. Hum. Gene Ther. 2002, 13, 3–13.CrossRefGoogle Scholar
  75. [75]
    Muruve, D. A. The innate immune response to adenovirus vectors. Hum. Gene Ther. 2004, 15, 1157–1166.CrossRefGoogle Scholar
  76. [76]
    Lai, C. Y.; Trewyn, B. G.; Jeftinija, D. M.; Jeftinija, K.; Xu, S.; Jeftinija, S.; Lin, V. S. A mesoporous silica nanospherebased carrier system with chemically removable CdS nanoparticle caps for stimuli-responsive controlled release of neurotransmitters and drug molecules. J. Am. Chem. Soc. 2003, 125, 4451–4459.CrossRefGoogle Scholar
  77. [77]
    Jin, S.; Ye, K. M. Nanoparticle-mediated drug delivery and gene therapy. Biotechnol. Prog. 2007, 23, 32–41.CrossRefGoogle Scholar
  78. [78]
    Mohr, R.; Kratz, K.; Weigel, T.; Lucka-Gabor, M.; Moneke, M.; Lendlein, A. Initiation of shape-memory effect by inductive heating of magnetic nanoparticles in thermoplastic polymers. P. Natl. Acad. Sci. USA 2006, 103, 3540–3545.CrossRefGoogle Scholar
  79. [79]
    Levy, L.; Sahoo, Y.; Kim, K. S.; Bergey, E. J.; Prasad, P. N. Nanochemistry: Synthesis and characterization of multifunctional nanoclinics for biological applications. Chem. Mater. 2002, 14, 3715–3721.CrossRefGoogle Scholar
  80. [80]
    Lu, C.; Hung, Y.; Hsiao, J. K.; Yao, M.; Chung, T. H.; Lin, Y. S.; Wu, S. H.; Hsu, S. C.; Liu, H. M.; Mou, C. Y; Yang, C. S.; Huang, D. M.; Chen, Y. C. Bifunctional magnetic silica nanoparticles for highly efficient human stem cell labeling. Nano Lett. 2007, 7, 149–154.CrossRefGoogle Scholar
  81. [81]
    Santra, S.; Bagwe, R. P.; Dutta, D.; Stanley, J. T.; Walter, G. A.; Tan, W. H.; Moudgil, B. M.; Mericle, R. A. Synthesis and characterization of fluorescent, radio-opaque and paramagnetic silica nanoparticles for multimodal bioimaging applications. Adv. Mater. 2005, 7, 2165–2169.CrossRefGoogle Scholar
  82. [82]
    Kircher, M. F.; Mahmood, U.; King, R. S.; Weissleder, R.; Josephson, L. A multimodal nanoparticle for preoperative magnetic resonance imaging and intraoperative optical brain tumor delineation. Cancer Res. 2003, 63, 8122–8125.Google Scholar
  83. [83]
    Lu, Y.; Yin, Y.; Mayers, B. T.; Xia, Y. Modifying the surface properties of superparamagnetic iron oxide nanoparticles through a Sol-Gel approach. Nano Lett. 2002, 2, 183–186.CrossRefGoogle Scholar
  84. [84]
    Jiang, W.; Kim, B. Y. S.; Rutka, J. T.; Chan, W. C. W. Nanoparticle-mediated cellular response is sizedependent. Nat. Nanotechnol. 2008, 3, 145–150.CrossRefGoogle Scholar
  85. [85]
    Gerashchenko, B. I.; Gun’ko, V. M.; Gerashchenko, I. I.; Mironyuk, I. F.; Leboda, R.; Hosoya, H. Probing the silica surfaces by red blood cells. Cytom. Part A 2002, 49, 56–61.CrossRefGoogle Scholar
  86. [86]
    Pomeroy, C.; Filice, G. A. Effect of intravenous silica on the course of Nocardia asteroids pneumonia. Infect. Immun. 1988, 56, 2507–2511.Google Scholar
  87. [87]
    Luo, D.; Saltzman, W. M. Nonviral gene delivery: Thinking of silica. Gene Ther. 2006, 13, 585–586.CrossRefGoogle Scholar

Copyright information

© Tsinghua Press and Springer-Verlag GmbH 2008

Authors and Affiliations

  1. 1.Lilly Research LaboratoriesEli Lilly and CompanyIndianapolisUSA
  2. 2.Chinese Academy of Inspection and QuarantineBeijingChina
  3. 3.Center for Research at the Bio/Nano Interface, Department of Chemistry and Department of Physiology and Functional Genomics, Shands Cancer Center, UF Genetics Institute and McKnight Brain InstituteUniversity of FloridaGainesvilleUSA

Personalised recommendations