Amphiphilic DNA Block Copolymers: Nucleic Acid-Polymer Hybrid Materials for Diagnostics and Biomedicine

  • Jan Zimmermann
  • Minseok Kwak
  • Andrew J. Musser
  • Andreas Herrmann
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 751)

Abstract

DNA-polymer conjugates have been recognized as versatile functional materials in many different fields ranging from nanotechnology to diagnostics and biomedicine. They combine the favorable properties of nucleic acids and synthetic polymers. Moreover, joining both structures with covalent bonds to form bioorganic hybrids allows for the tuning of specific properties or even the possibility of evolving completely new functions. One important class of this type of material is amphiphilic DNA block copolymers, which, due to microphase separation, can spontaneously adopt nanosized micelle morphologies with a hydrophobic core and a DNA corona. These DNA nano-objects have been explored as vehicles for targeted gene and drug delivery, and also as programmable nanoreactors for organic reactions. Key to the successful realization of these potential applications is that (1) DNA block copolymer conjugates can be fabricated in a fully automated fashion by employing a DNA synthesizer; (2) hydrophobic compounds can be loaded within their interior; and (3) they can be site-specifically functionalized by a convenient nucleic acid hybridization procedure. This chapter aims to broaden the range of biodiagnostic and biomedical applications of these materials by providing a comprehensive outline of the preparation and characterization of multifunctional DNA-polymer nanoparticles.

Key words

DNA Block copolymers Nanoparticles Oligonucleotides Drug delivery Anticancer drug Macromolecular amphiphiles Solid-phase synthesis 

References

  1. 1.
    Lemaitre M., Bayard B., Lebleu B. (1987) Specific antiviral activity of a poly(L-lysine)-conjugated oligodeoxyribonucleotide sequence complementary to vesicular stomatitis virus N protein mRNA initiation site. Proc. Natl. Acad. Sci. USA 84, 648–52.PubMedCrossRefGoogle Scholar
  2. 2.
    Yang C. Y. J., Pinto M., Schanze K., Tan W. H. (2005) Direct synthesis of an oligonucleotide-poly(phenylene ethynylene) conjugate with a precise one-to-one molecular ratio. Angew. Chem. Int. Ed. 44, 2572–6.CrossRefGoogle Scholar
  3. 3.
    Costioli M. D., Fisch I., Garret-Flaudy F., Hilbrig F., Freitag R. (2003) DNA purification by triple-helix affinity precipitation. Biotechnol. Bioeng. 81, 535–45.PubMedCrossRefGoogle Scholar
  4. 4.
    Soh N., Umeno D., Tang Z. L., Murata M., Maeda M. (2002) Affinity precipitation separation of DNA binding protein using block conjugate composed of poly(N-isopropyla­crylamide) grafted double-stranded DNA and double-stranded DNA containing a target sequence. Anal. Sci. 18, 1295–9.PubMedCrossRefGoogle Scholar
  5. 5.
    The Eyetec Study Group (2002) Preclinical and phase 1A clinical evaluation of an anti-VEGF pegylated aptamer (EYE001) for the treatment of exudative age-related macular degeneration. Retina 22, 143–52.CrossRefGoogle Scholar
  6. 6.
    Oishi M., Nagatsugi F., Sasaki S., Nagasaki Y., Kataoka K. (2005) Smart polyion complex micelles for targeted intracellular delivery of PEGylated antisense oligonucleotides containing acid-labile linkages. ChemBioChem 6, 718–25.PubMedCrossRefGoogle Scholar
  7. 7.
    Jeong J. H., Kim S. W., Park T. G. (2003) A new antisense oligonucleotide delivery system based on self-assembled ODN-PEG hybrid conjugate micelles. J. Control. Release 183–91.Google Scholar
  8. 8.
    Kim S. H., Jeong J. H., Lee S. H., Kim S. W., Park T. G. (2008) Local and systemic delivery of VEGF siRNA using polyelectrolyte complex micelles for effective treatment of cancer. J. Control. Release 129, 107–16.PubMedCrossRefGoogle Scholar
  9. 9.
    Alemdaroglu F. E., Herrmann A. (2007) DNA meets synthetic polymers – highly versatile hybrid materials. Org. Biomol. Chem. 5, 1311–20.PubMedCrossRefGoogle Scholar
  10. 10.
    Alemdaroglu F. E., Ding K., Berger R., Herrmann A. (2006) DNA-templated synthesis in three dimensions: Introducing a micellar scaffold for organic reactions. Angew. Chem. Int. Ed. 45, 4206–10.CrossRefGoogle Scholar
  11. 11.
    Safak M., Alemdaroglu F. E., Li Y., Ergen E., Herrmann A. (2007) Polymerase chain reaction as an efficient tool for the preparation of block copolymers. Adv. Mater. 19 1499–505.CrossRefGoogle Scholar
  12. 12.
    Alemdaroglu F. E., Zhuang W., Zöphel L., et al. (2009) Generation of Multiblock copolymers by PCR: synthesis, visualization and nanomechanical properties. Nano Lett. 9, 3658–62.PubMedCrossRefGoogle Scholar
  13. 13.
    Ding K., Alemdaroglu F. E., Börsch M., Berger R., Herrmann A. (2007) Engineering the structural properties of DNA block copolymer micelles by molecular recognition. Angew. Chem. Int. Ed. 46, 1172–5.CrossRefGoogle Scholar
  14. 14.
    Alemdaroglu F. E., Wang J., Börsch M., Berger R., Herrmann A. (2008) Enzymatic control of the size of DNA block copolymer nanoparticles. Angew. Chem. Int. Ed. 47, 974–6.CrossRefGoogle Scholar
  15. 15.
    Alemdaroglu F. E., Alemdaroglu C. N., Langguth P., Herrmann A. (2008) Shape dependent cellular uptake of dna nanoparticles. Macromol. Rapid. Commun. 29, 326–9.CrossRefGoogle Scholar
  16. 16.
    Alemdaroglu F. E., Alemdaroglu C. N., Langguth P., Herrmann A. (2008) DNA Block copolymer micelles - A combinatorial tool for cancer nanotechnology. Adv. Mat. 20, 899–902.CrossRefGoogle Scholar
  17. 17.
    The Sourcebook – A Handbook for Gel Electrophoresis, Cambrex Bio Science Rockland, Inc., Rockland, MAGoogle Scholar
  18. 18.
    Shuai X. T., Ai H., Nasongkla N., Kim S., Gao J. M. (2004) Micellar carriers based on block copolymers of poly(ε-caprolactone) and poly(ethylene glycol) for doxorubicin delivery. J. Control. Release 98, 415–26.PubMedCrossRefGoogle Scholar
  19. 19.
    Integrated DNA Technologies, Inc. web-based calculator for molar extinction coefficients of ODNs http://biophysics.idtdna.com/.

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Jan Zimmermann
  • Minseok Kwak
  • Andrew J. Musser
  • Andreas Herrmann
    • 1
  1. 1.Department of Polymer Chemistry, The Zernike Institute for Advanced MaterialsUniversity of GroningenGroningenThe Netherlands

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