Skip to main content
Log in

Combinatorial targeting and nanotechnology applications

  • Published:
Biomedical Microdevices Aims and scope Submit manuscript

Abstract

The development of improved methods for targeted cell detection is of general interest in many fields of research and drug development. There are a number of well-established techniques for the study and detection of biomarkers expressed in living cells and tissues. Many of them rely on multi-step procedures that might not meet ideal assay requirements for speed, cost, sensitivity, and specificity. Here we report and further validate an approach that enables spontaneous molecular assembly to generate biologically active networks of bacteriophage (phage) assembled with gold (Au) nanoparticles (termed Au-phage nanoshuttles). Here, the nanoshuttles preserve the cell binding and internalization attributes mediated by a displayed peptide targeted to a cell surface receptor. The organization of such targeted assemblies can be further manipulated to be used as a mutimodal detection assembly, and they can be characterized as fractal nanostructures by angle-dependent light scattering fractal dimension analysis. Targeted Au-phage nanoshuttles offer multiple functionalities for nanotechnology-based sensing and reporting, including enhanced florescence and improved contrast for darkfield microscopy.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • W. Arap, R. Pasqualini, E. Ruoslahti, Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science 279, 377–380 (1998)

    Article  Google Scholar 

  • W. Arap et al., Steps toward mapping the human vasculature by phage display. Nat. Med. 8, 121–7 (2002)

    Article  Google Scholar 

  • P.W. Atkins, Physical chemistry (W. H. Freeman and Company, New York, 1990)

    Google Scholar 

  • D. Avnir, D. Farin, P. Pfeifer, Molecular fractal surfaces. Nature 308, 261–263 (1984)

    Article  Google Scholar 

  • T. Bacarese-Hamilton, F. Bistoni, A. Crisanti, Protein microarrays: from serodiagnosis to whole proteome scale analysis of the immune response against pathogenic microorganisms. Biotechniques 33, S24–9 (2002)

    Google Scholar 

  • A.L. Barabasi, H.E. Stanley, Fractal concepts in surface growth (Cambridge University Press, 1995)

  • C.F. Barbas III, D.R. Burton, J.K. Scott, G.J. Silverman, Phage display, a laboratory manual (Cold Spring Harbor Laboratory Press, New York, 2001)

    Google Scholar 

  • A.M. Brasil, T.L. Farias, M.G. Carvalho, Evaluation of the fractal properties of cluster-cluster aggregates. Aerosol. Sci. Technol. 33, 440–454 (2000)

    Article  Google Scholar 

  • T.G. Dewey, Fractals in molecular biophysics (Oxford University Press, New York, 1997)

    MATH  Google Scholar 

  • J. Dutta, H. Hofmann, in Encyclopedia of Nanoscience and Nanotechnology, ed. H.S. Nalwa (American Scientific Publishers, Stevenson Ranch, CA, 2003), pp. 1–23

  • T.L. Farias, U.O. Koylu, M.G. Carvalho, Range of validity of the Rayleigh-Debye-Gans theory for optics of fractal aggregates. Appl. Opt. 35, 6560–6567 (1996)

    Article  Google Scholar 

  • R.J. Giordano, M. Cardo-Vila, J. Lahdenranta, R. Pasqualini, W. Arap, Biopanning and rapid analysis of selective interactive ligands. Nat. Med. 7, 1249–1253 (2001)

    Article  Google Scholar 

  • D.A. Handley, in Colloidal gold: Principles, methods, and applications, ed. M.A. Hayat (Academic Press, San Diego, 1989), pp. 23–27

  • E. Harlow, D. Lane, Using antibodies: A laboratory manual (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 1999)

    Google Scholar 

  • M.G. Kolonin, P.K. Saha, L. Chan, R. Pasqualini, W. Arap, Reversal of obesity by targeted ablation of adipose tissue. Nat. Med. 10, 625–632 (2004)

    Article  Google Scholar 

  • S.S. Krishnan, K.C. Lin, G.M. Faeth, Optical properties in the visible of overfire soot in large buoyant turbulent diffusion flames. J. Heat Transf. 122, 517–524 (2000)

    Article  Google Scholar 

  • R. Langer, D.A. Tirrell, Designing materials for biology and medicine. Nature 428, 487–492 (2004)

    Article  Google Scholar 

  • R.R. Langley et al., Tissue-specific microvascular endothelial cell lines from H-2 K(b)-tsA58 mice for studies of angiogenesis and metastasis. Cancer Res. 63, 2971–6 (2003)

    Google Scholar 

  • D.A. LaVan, D.M. Lynn, R. Langer, Moving smaller in drug discovery and delivery. Nat. Rev. Drug. Discov. 1, 77–84 (2002)

    Article  Google Scholar 

  • E.R. Leite, in Encyclopedia of Nanoscience and Nanotechnology, ed. H.S. Nalwa (American Scientific Publishers, Stevenson Ranch, CA, 2004), pp. 537–554.

  • B.B. Mandelbrot, The fractal geometry of nature (Freeman, San Francisco, 1982)

    MATH  Google Scholar 

  • C.A. Mirkin, R.L. Letsinger, R.C. Mucic, J.J. Storhoff, A DNA-based method for rationally assembling nanoparticles into macroscopic materials. Nature 382, 607–609 (1996)

    Article  Google Scholar 

  • C. Oh, C.M. Sorensen, Structure factor of diffusion-limited aggregation clusters: local structure and non-self-similarity. Phys. Rev. E 57, 784–790 (1998)

    Article  Google Scholar 

  • R. Pasqualini, W. Arap, in Encyclopedia of Cancer, ed. J.R. Bertino (Academic Press, San Diego-Oxford, 2002), pp. 501–507

  • K.R. Purdy, S. Fraden, Isotropic-cholesteric phase transition of filamentous virus suspensions as a function of rod length and charge. Phys. Rev. E 70, 061703-1–061703-8 (2004)

    Article  Google Scholar 

  • M. Schroeder, Fractals, chaos, power laws: Minutes from an infinite paradise (W. H. Freeman and Company, New York, 1992)

    Google Scholar 

  • T.G. Smith Jr., G.D. Lange, W.B. Marks, Fractal methods and results in cellular morphology-dimensions, lacunarity and multifractals. J. Neurosci. Methods 69, 123–126 (1996)

    Article  Google Scholar 

  • C.M. Sorensen, N. Lu, J. Cai, Fractal cluster size distribution measurement using static light scattering. J. Colloid and Interface Sci. 174, 456–460 (1995)

    Article  Google Scholar 

  • G.R. Souza, J.H. Miller, Oligonucleotide detection using angle-dependent light scattering and fractal dimension analysis of gold-DNA aggregates. J. Am. Chem. Soc. 123, 6734–6735 (2001)

    Article  Google Scholar 

  • G.R. Souza, in Chemistry (The George Washington University, Washington, DC, 2004), pp. 276

  • G.R. Souza et al., Networks of gold nanoparticles and bacteriophage as biological sensors and cell targeting agents. Proc. Natl. Acad. Sci. USA 103, 1215–1220 (2006a)

    Article  Google Scholar 

  • G.R. Souza et al., In vivo detection of gold-imidazole self-assembly complexes: NIR-SERS signal reporters. Anal. Chem. 78, 6232–6237 (2006b)

    Article  Google Scholar 

  • G.R. Souza, J.H. Miller, in Annual Reviews in Plasmonics, ed. C. Geddes (Kluwer Academic/Plenum, New York, 2006)

  • M. Trepel, W. Arap, R. Pasqualini, In vivo phage display and vascular heterogeneity: implications for targeted medicine. Curr. Opin. Chem. Biol. 6, 399–404 (2002)

    Article  Google Scholar 

  • D.A. Weitz, J.S. Huang, M.Y. Lin, J. Sung, Limits of the fractal dimension for irreversible kinetic aggregation of gold colloids. Phys. Rev. Lett. 54, 1416–1419 (1985)

    Article  Google Scholar 

  • G.B. West, J.H. Brown, B.J. Enquist, The fourth dimension of life: fractal geometry and allometric scaling of organisms. Science 284, 1677–9 (1999)

    Article  MathSciNet  Google Scholar 

  • J. Yguerabide, E.E. Yguerabide, Light-scattering submicroscopic particles as highly fluorescent analogs and their use as tracer labels in clinical and biological applications. I. Theory. Anal. Biochem. 262, 137–156 (1998a)

    Article  Google Scholar 

  • J. Yguerabide, E.E. Yguerabide, Light-scattering submicroscopic particles as highly fluorescent analogs and their use as tracer labels in clinical and biological applications. II. Experimental characterization. Anal. Biochem. 262, 157–176 (1998b)

    Article  Google Scholar 

Download references

Acknowledgements

G.S. is a Scholar from the Odyssey Program at The University of Texas M.D. Anderson Cancer Center. This work was supported by a grant from the Department of Defense (to G.S.) and by an award from the Gillson–Longenbaugh Foundation (to W.A. and R.P.).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Renata Pasqualini or Wadih Arap.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Souza, G.R., Staquicini, F.I., Christianson, D.R. et al. Combinatorial targeting and nanotechnology applications. Biomed Microdevices 12, 597–606 (2010). https://doi.org/10.1007/s10544-009-9340-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10544-009-9340-6

Keywords

Navigation