Advertisement

Colloid and Polymer Science

, Volume 283, Issue 11, pp 1197–1205 | Cite as

Complexation of well-controlled low-molecular weight polyelectrolytes with antisense oligonucleotides

  • Jane Jin
  • John C. Achenbach
  • Shiping ZhuEmail author
  • Yingfu Li
Original contribution

Abstract

The influences of polymer-related properties such as molecular weight, charge density, counter ion, and hydrophilic block on the complexation of polyelectrolytes and a fluorescein-labeled oligonucleotide (ON) were investigated. A series of well-defined and well-controlled 2-(N,N-dimethylamino)ethyl methacrylate (DMAEMA) polymers and block copolymers were prepared using living anionic and radical polymerization methods. Fluorescence measurement was used to reveal the effects of polymer molecular weight, charge density, and counter ion type on the complexation. PolyDMAEMA samples having double molecular weights of the chosen oligonucleotide gave the optimal complexation performance. Kinetic studies showed that high-molecular weight/high-charge density polymer samples produced very stable complexes. The fully charged polyDMAEMA displayed the strongest binding with the ON. These complexes were therefore less sensitive to the changes in the environment. PolyDMAEMA–DMSQ samples had slightly higher complexation ability than polyDMAEMA–MCQ (DMSQ: dimethylsulfate quat; MCQ: methylchloride quat). Both poly(DMAEMA-b-HEMA) and poly(DMAEMA–MCQ-b-PEG) block copolymers showed good complexation ability and steric stability [HEMA: 2-hydroxyethyl methacrylate; PEG: poly(ethylene glycol)]. PEG, but not HEMA block, enhanced the effectiveness of polyDMAEMA–MCQ binding with the ON.

Keywords

Polyelectrolytes Complexation Antisense oligonucleotides Polymer vector Delivery Living polymerization 

Notes

Acknowledgements

We would like to thank the Natural Science and Engineering Research Council of Canada (NSERC) and Canadian Foundation for Innovation (CFI) for the financial supports to both SZ and YL. We also thank Prof. S.P. Armes University of Sussex, UK for donating the PolyDMAEMA–MCQ and PolyDMAEMA–MCQ-b-PEO samples. JJ and JA would like to express their appreciations to the Ontario Ministry of Education and NSERC, respectively, for an OGS scholarship and an NSERC PGS A scholarship.

References

  1. 1.
    Zamecnik PC, Stephenson ML (1978) Proc Natl Acad Sci USA 75:280CrossRefGoogle Scholar
  2. 2.
    Schell PL (1974) Biochim Biophys Acta 340:323Google Scholar
  3. 3.
    Wu GY, Wu CH (1992) J Biol Chem 267:12436Google Scholar
  4. 4.
    Leonetti JP, Rayner B, Lemaitre M, Gagnor C, Milhaud PG, Imbach JL, Lebleu B (1998) Gene 72:323CrossRefGoogle Scholar
  5. 5.
    Leonetti JP, Degols G, Lebleu B (1990) Bioconj Chem 1:149CrossRefGoogle Scholar
  6. 6.
    Boussif O, Lezoualch F, Zanta MA, Mergny MD, Scherman D, Demeneix B, Behr J (1995) Proc Natl Acad Sci USA 92:7297CrossRefGoogle Scholar
  7. 7.
    Dheur S, Dias N, van Aerschot A, Herdewijn P, Bettinger T, Remy JS, Jelene C, Saison-Behmoaras ET (1999) Antisense Nucleic Acid Drug Dev 9:515CrossRefGoogle Scholar
  8. 8.
    van Rompaey E, Sanders N, De Smedt SC, Demeester J (2000) Macromolecules 33:8280CrossRefGoogle Scholar
  9. 9.
    van Rompaey E, Engelborghs Y, Sanders N, De Smedt SC, Demeester J (2001) Pharm Res 18:928CrossRefGoogle Scholar
  10. 10.
    van Rompaey E, Chen Y, Mûller JD, Gratton E, van Craenenbroedk E, Engelborghs Y, De Smedt S (2001) Demeester J Biol Chem 382:379CrossRefGoogle Scholar
  11. 11.
    Kabanov AV, Vinogradov SV, Suzdaltseva YG, Alakhov VY (1995) Bioconjugate Chem 6:639CrossRefGoogle Scholar
  12. 12.
    Kataoka K, Togawa H, Harada A, Yasugi K, Matsumoto T, Katayose S (1996) Macromolecules 29:8556CrossRefGoogle Scholar
  13. 13.
    Read ML, Dash PR, Clark A, Howard KA, Oupicky D, Toncheva V, Alpar HO, Schacht EH, Ulbrich K, Seymour LW (2000) Euro J Pharm Sci 10:169CrossRefGoogle Scholar
  14. 14.
    Deshpande MC, Garnett MC, Vamvakaki M, Bailey L, Armes SP, Stolnik S (2002) J Control Release 81:185CrossRefGoogle Scholar
  15. 15.
    Zhang ZR, Liu G, Bell S (2000) Macromolecules 33:7877CrossRefGoogle Scholar
  16. 16.
    Shen Y, Zeng F, Zhu S, Pelton R (2001) Macromoleculaes 34:144CrossRefGoogle Scholar
  17. 17.
    Zeng F, Shen Y Zhu S, Pelton R (2000) J Polym Sci Polym Chem 38:3821CrossRefGoogle Scholar
  18. 18.
    Shen Y, Zeng F, Zhu S, Pelton R (2000) Macromolecules 33:5399CrossRefGoogle Scholar
  19. 19.
    Zeng F, Shen Y, Zhu S, Pelton R (2000) Macromoleculs 33:1628CrossRefGoogle Scholar
  20. 20.
    Li Y, Armes SP, Jin J, Zhu S (2003) Macromolecules 36:8286Google Scholar
  21. 21.
    Wang XS, Armes SP (2000) Macromolecules 33:6640CrossRefGoogle Scholar
  22. 22.
    Lakowicz JR (1999) Principles of fluorescence spectroscopy 2nd edition. Kluwer Academic/Plenum Publishers, New YorkGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Jane Jin
    • 1
  • John C. Achenbach
    • 2
  • Shiping Zhu
    • 1
    Email author
  • Yingfu Li
    • 2
  1. 1.Department of Chemical EngineeringMcMaster UniversityHamiltonCanada
  2. 2.Department of BiochemistryMcMaster UniversityHamiltonCanada

Personalised recommendations