Skip to main content
SpringerLink
Log in

Tuning with Phosphorylcholine Grafts Improves the Physicochemical Properties of PLL/pDNA Nanoparticles at Neutral pH

  • Article
  • Published:
Macromolecular Research Aims and scope Submit manuscript

Abstract

The improvement of biological properties of polycations is a fundamental step to overcome their limitations as non-viral gene carriers. This work studied the effect of phosphorylcholine (PC) groups on the physicochemical properties of poly(L-lysine) (PLL)/pDNA nanoparticles. Phosphorylcholine-grafted PLL derivatives (PLL-PC) containing increasing proportions of PC were obtained by the reductive amination reaction with phosphoryl glyceraldehyde and characterized by 1H NMR, FTIR, and GPC measurements. The PLL-PC derivatives were used to prepare polyplexes with pDNA and their properties were evaluated by fluorescence, gel electrophoresis and dynamic light scattering (DLS) measurements. The PLL-PC derivatives were able to interact with pDNA at low N/P ratios in physiological pH to form stable polyplexes having lower zeta potentials, as evidenced by the gel electrophoresis and zeta potentials measurements. A degree of grafting of 10% increased the in vitro transfection efficiency of PLL and a degree of 20 mol% of PC groups provided colloidal stability in physiological saline solution at neutral pH. Overall, the PC-PLL derivatives exhibited improved physicochemical properties and have significant potential for further studies as non-viral gene transfer agents.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. H. Yin, R. L. Kanasty, A. A. Eltoukhy, A. J. Vegas, J. R. Dorkin, and D. G. Anderson, Nat. Rev. Genet., 15, 541 (2014).

    CAS  PubMed  Google Scholar 

  2. Y. Zhang, A. Satterlee, and L. Huang, Mol. Ther., 20, 1298 (2012).

    CAS  PubMed Central  PubMed  Google Scholar 

  3. H. Eliyahu, Y. Barenholz, and A. J. Domb, Molecules, 10, 34 (2005).

    CAS  PubMed Central  PubMed  Google Scholar 

  4. M. Morille, C. Passirani, A. Vonarbourg, A. Clavreul, and J. P. Benoit, Biomaterials, 29, 3477 (2008).

    CAS  PubMed  Google Scholar 

  5. P. R. Dash, M. L. Read, L. B. Barrett, M. Wolfert, and L. W. Seymour, Gene Ther., 6, 643 (1999).

    CAS  PubMed  Google Scholar 

  6. C. M. Ward, M. L. Read, and L. W. Seymour, Blood, 97, 2221 (2001).

    CAS  PubMed  Google Scholar 

  7. K. Miyata, M. Oba, M. R. Kano, S. Fukushima, Y. Vachutinsky, M. Han, H. Koyama, K. Miyazono, N. Nishiyama, and K. Kataoka, Pharm. Res., 25, 2924 (2008).

    CAS  PubMed  Google Scholar 

  8. M. Oishi, H. Hayashi, K. Itaka, K. Kataoka, and Y. Nagasaki, Colloid Polym. Sci., 285, 1055 (2007).

    CAS  Google Scholar 

  9. S. Barati, P. R. Hurtado, S. H. Zhang, R. Tinsley, I. A. Ferguson, and R. A. Rush, Exp. Neurol., 202, 179 (2006).

    CAS  PubMed  Google Scholar 

  10. Y. Nie, Z. R. Zhang, L. Li, K. Luo, H. Ding, and Z. W. Gu, J. Mater. Sci. Mater. Medicine, 20, 1849 (2009).

    CAS  Google Scholar 

  11. T. Wada, A. Kano, N. Shimada, and A. Maruyama, Macromol. Res., 20, 302 (2012).

    CAS  Google Scholar 

  12. M. S. Shim and Y. J. Kwon, Biomaterials, 31, 3404 (2010).

    CAS  PubMed  Google Scholar 

  13. D. Y. Kwoh, C. C. Coffin, C. P. Lollo, J. Jovenal, M. G. Banaszczyk, P. Mullen, A. Phillips, A. Amini, J. Fabrycki, R. M. Bartholomew, S. W. Brostoff, and D. J. Carlo, BBA-Gene Struct. Expr., 1444, 171 (1999).

    CAS  Google Scholar 

  14. M. Rimann, T. Luhmann, M. Textor, B. Guerino, J. Ogier, and H. Hall, Bioconjugate Chem., 19, 548 (2008).

    CAS  Google Scholar 

  15. M. Abbasi, H. Uludag, V. Incani, C. Y. M. Hsu, and A. Jeffery, Biomacromolecules, 9, 1618 (2008).

    CAS  PubMed  Google Scholar 

  16. K. Miyata, Y. Kakizawa, N. Nishiyama, A. Harada, Y. Yamasaki, H. Koyama, and K. Kataoka, J. Am. Chem. Soc., 126, 2355 (2004).

    CAS  PubMed  Google Scholar 

  17. M. Oba, Y. Vachutinsky, K. Miyata, M. R. Kano, S. Ikeda, N. Nishiyama, K. Itaka, K. Miyazono, H. Koyama, and K. Kataoka, Mol. Pharm., 7, 501 (2010).

    CAS  PubMed  Google Scholar 

  18. J. S. Park, J. K. Park, J. P. Nam, W. S. Kim, C. Choi, M. Y. Kim, M. K. Jang, and J. W. Nah, Macromol. Res., 20, 667 (2012).

    CAS  Google Scholar 

  19. M. J. Yim, J. E. Kim, C. H. Ahn, H. A. Kim, M. Lee, and S. Y. Chae, Macromol. Res., 18, 545 (2010).

    CAS  Google Scholar 

  20. R. G. Thomas, M. Muthiah, M. Moon, I. K. Park, and Y. Y. Jeong, Macromol. Res., 25, 446 (2017).

    CAS  Google Scholar 

  21. A. L. Lewis and A. W. Lloyd, in Biomimetic, Bioresponsive, and Bioactive Materials: An Introduction to Integrating Materials with Tissues, M. Santin and G. Phillips, Eds., John Wiley & Sons, Inc., 2012, pp 95–140.

  22. J. P. Salvage, C. Thom, A. L. Lewis, G. J. Phillips, and A. W. Lloyd, J. Mater. Sci.-Mater. M., 26 (2015).

  23. M. Ahmed, M. Jawanda, K. Ishihara, and R. Narain, Biomaterials, 33, 7858 (2012).

    CAS  PubMed  Google Scholar 

  24. A. H. Case, I. P. D. Picola, M. E. D. Zaniquelli, J. C. Fernandes, S. R. Taboga, F. M. Winnik, and M. J. Tiera, J. Colloid Interf. Sci., 336, 125 (2009).

    CAS  Google Scholar 

  25. Y. T. A. Chim, J. K. W. Lam, Y. Ma, S. P. Armes, A. L. Lewis, C. J. Roberts, S. Stolnik, S. J. B. Tendler, and M. C. Davies, Langmuir, 21, 3591 (2005).

    CAS  PubMed  Google Scholar 

  26. M. Q. Tan, Y. K. Feng, H. Y. Wang, L. Zhang, M. Khan, J. T. Guo, Q. L. Chen, and J. S. Liu, Macromol. Res., 21, 541 (2013).

    CAS  Google Scholar 

  27. M. J. Tiera, X. P. Qiu, S. Bechaouch, Q. Shi, J. C. Fernandes, and F. M. Winnik, Biomacromolecules, 7, 3151 (2006).

    CAS  PubMed  Google Scholar 

  28. K. Miyazawa and F. M. Winnik, Macromolecules, 35, 9536 (2002).

    CAS  Google Scholar 

  29. K. Corsi, F. Chellat, L. Yahia, and J. C. Fernandes, Biomaterials, 24, 1255 (2003).

    CAS  PubMed  Google Scholar 

  30. B. Lu, X. D. Xu, X. Z. Zhang, S. X. Cheng, and R. X. Zhuo, Biomacromolecules, 9, 2594 (2008).

    CAS  PubMed  Google Scholar 

  31. R. J. Wittebort, A. Szabo, and F. R. N. Gurd, J. Am. Chem. Soc., 102, 5723 (1980).

    CAS  Google Scholar 

  32. A. Reisch, J. C. Voegel, G. Decher, P. Schaaf, and P. J. Mesini, Macromol. Rapid Commun., 28, 2217 (2007).

    CAS  Google Scholar 

  33. A. Dos, V. Schimming, S. Tosoni, and H. H. Limbach, J. Phys. Chem. B, 112, 15604 (2008).

    CAS  PubMed  Google Scholar 

  34. J. J. Sun, T. Luo, R. L. Sheng, H. Li, S. D. Chen, F. Z. Hu, and A. M. Cao, Macromol. Biosci., 13, 35 (2013).

    CAS  PubMed  Google Scholar 

  35. V. Toncheva, M. A. Wolfert, P. R. Dash, D. Oupicky, K. Ulbrich, L. W. Seymour, and E. H. Schacht, BBA-Gen. Subjects, 1380, 354 (1998).

    CAS  Google Scholar 

  36. H. Lomas, J. Z. Du, I. Canton, J. Madsen, N. Warren, S. P. Armes, A. L. Lewis, and G. Battaglia, Macromol. Biosci., 10, 513 (2010).

    CAS  PubMed  Google Scholar 

  37. J. F. Guo, W. P. Cheng, J. X. Gu, C. X. Ding, X. Z. Qu, Z. Z. Yang, and C. O’Driscoll, Eur. J. Pharm. Sci., 45, 521 (2012).

    CAS  PubMed  Google Scholar 

  38. I. P. Dalla Picola, K. A. N. Busson, A. H. Case, F. D. Nasario, V. A. D. Tiera, S. R. Taboga, J. R. Neto, and M. J. Tiera, J. Exp. Nanosci., 8, 539 (2013).

    Google Scholar 

  39. S. P. Strand, S. Lelu, N. K. Reitan, C. D. Davies, P. Artursson, and K. M. Varum, Biomaterials, 31, 975 (2010).

    CAS  PubMed  Google Scholar 

  40. R. J. Smith, R. W. Beck, and L. E. Prevette, Biophys. Chem., 203, 12 (2015).

    PubMed  Google Scholar 

  41. A. Mann, R. Richa, and M. Ganguli, J. Control. Release, 125, 252 (2008).

    CAS  PubMed  Google Scholar 

  42. M. I. Nounou, K. Emmanouil, S. Chung, T. Pham, Z. Y. Lu, and M. Bikram, J. Control. Release, 143, 326 (2010).

    CAS  PubMed  Google Scholar 

  43. L. N. Chen, H. B. Wang, Y. F. Zhang, Y. X. Wang, Q. L. Hu, and J. Ji, Colloids Surf. B, 111, 297 (2013).

    CAS  Google Scholar 

  44. L. J. Arnold, A. Dagan, J. Gutheil, and N. O. Kaplan, Proc. Natl. Acad. Sci. U.S.A., 76, 3246 (1979).

    CAS  PubMed Central  PubMed  Google Scholar 

  45. Z. Kadlecova, L. Baldi, D. Hacker, F. M. Wurm, and H. A. Klok, Biomacromolecules, 13, 3127 (2012).

    CAS  PubMed  Google Scholar 

  46. I. R. C. Hill, M. C. Garnett, F. Bignotti, and S. S. Davis, BBA-Gen. Subjects, 1427, 161 (1999).

    CAS  Google Scholar 

  47. P. Symonds, J. C. Murray, A. C. Hunter, G. Debska, A. Szewczyk, and S. M. Moghimi, FEBS Lett., 579, 6191 (2005).

    CAS  PubMed  Google Scholar 

  48. M. Thibault, S. Nimesh, M. Lavertu, and M. D. Buschmann, Mol. Ther., 18, 1787 (2010).

    CAS  PubMed Central  PubMed  Google Scholar 

  49. J. Sun, F. Zeng, H. L. Jian, and S. Z. Wu, Polym. Chem.-UK, 4, 5810 (2013).

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departamento de Química e Ciências Ambientáis, UNESP-Universidade Estadual Paulista, São Paulo, Brasil

    Juliana Semensato, Vera Aparecida de Oliveira Tiera, Aline Margarete Furuyama Lima & Marcio José Tiera

  2. Orthopedic Research Laboratory, Hôpital du Sacré-Coeur de Montréal, Université de Montréal, Montréal, Canada

    Juliana Semensato, Júlio Cesar Fernandes & Mohamed Benderdour

Authors
  1. Juliana Semensato
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Júlio Cesar Fernandes
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mohamed Benderdour
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vera Aparecida de Oliveira Tiera
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Aline Margarete Furuyama Lima
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marcio José Tiera
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marcio José Tiera.

Additional information

Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Acknowledgments: M. J. Tiera would like to thank the São Paulo Research Foundation (FAPESP - Fundação de Amparo à Pesquisa do Estado de São Paulo) and the National Council for Scientific and Technological Development (CNPq) (Grant 2014/407499). A. M. F. Lima and A. M. M. Junior thank the National Council for the Improvement of Higher Education (CAPES) for its support (Grants PNPD 1267244, finance code 001 and 1743469). The authors report no conflicts of interest in this work. The authors would also like to thank L. F. M. Ferraz (Embrapa Instrumentação-São Carlos) for help with the Scanning Electron Microscopy, M. P. S. Cabrera (Peptides Research Group-UNESP, Grant FAPESP 2012/24259-0) and C. R. Bonini Domingos for access to instrumentation.

Supporting Information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Semensato, J., Fernandes, J.C., Benderdour, M. et al. Tuning with Phosphorylcholine Grafts Improves the Physicochemical Properties of PLL/pDNA Nanoparticles at Neutral pH. Macromol. Res. 28, 126–135 (2020). https://doi.org/10.1007/s13233-020-8019-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13233-020-8019-y

Keywords

Search

Navigation