Display options
Cite
Melamed JR, Kreuzberger NL, Goyal R, et al. Spherical Nucleic Acid Architecture Can Improve the Efficacy of Polycation-Mediated siRNA Delivery. Mol Ther Nucleic Acids. 2018;12:207-219doi: 10.1016/j.omtn.2018.05.008.
Melamed, J. R., Kreuzberger, N. L., Goyal, R., & Day, E. S. (2018). Spherical Nucleic Acid Architecture Can Improve the Efficacy of Polycation-Mediated siRNA Delivery. Molecular therapy. Nucleic acids, 12207-219. https://doi.org/10.1016/j.omtn.2018.05.008
Melamed, Jilian R, et al. "Spherical Nucleic Acid Architecture Can Improve the Efficacy of Polycation-Mediated siRNA Delivery." Molecular therapy. Nucleic acids vol. 12 (2018): 207-219. doi: https://doi.org/10.1016/j.omtn.2018.05.008
Melamed JR, Kreuzberger NL, Goyal R, Day ES. Spherical Nucleic Acid Architecture Can Improve the Efficacy of Polycation-Mediated siRNA Delivery. Mol Ther Nucleic Acids. 2018 Sep 07;12:207-219. doi: 10.1016/j.omtn.2018.05.008. Epub 2018 Jun 02. PMID: 30195760; PMCID: PMC6023847.
Copy Download .nbib Format: NLM
Share it on

Mol Ther Nucleic Acids. 2018 Sep 07;12:207-219. doi: 10.1016/j.omtn.2018.05.008. Epub 2018 Jun 02.

Spherical Nucleic Acid Architecture Can Improve the Efficacy of Polycation-Mediated siRNA Delivery.

Molecular therapy. Nucleic acids

Jilian R Melamed, Nicole L Kreuzberger, Ritu Goyal, Emily S Day

Affiliations

  1. Biomedical Engineering, University of Delaware, Newark, DE 19716, USA.
  2. Biomedical Engineering, University of Delaware, Newark, DE 19716, USA; Materials Science & Engineering, University of Delaware, Newark, DE 19716, USA; Helen F. Graham Cancer Center and Research Institute, Newark, DE 19713, USA. Electronic address: [email protected].

PMID: 30195760 PMCID: PMC6023847 DOI: 10.1016/j.omtn.2018.05.008

Abstract

Clinical translation of small interfering RNA (siRNA) nanocarriers is hindered by limited knowledge regarding the parameters that regulate interactions between nanocarriers and biological systems. To address this, we investigated the influence of polycation-based nanocarrier architecture on intracellular siRNA delivery. We compared the cellular interactions of two polycation-based siRNA carriers that have similar size and surface charge but different siRNA orientation: (1) polyethylenimine-coated spherical nucleic acids (PEI-SNAs), in which polyethylenimine is wrapped around a spherical nucleic acid core containing radially oriented siRNA and (2) randomly assembled polyethylenimine-siRNA polyplexes that lack controlled architecture. We found that PEI-SNAs undergo enhanced and more rapid cellular uptake than polyplexes, suggesting a prominent role for architecture in cellular uptake. Confocal microscopy studies demonstrated that while PEI-SNAs and polyplexes exhibit similar intracellular stability, PEI-SNAs undergo decreased accumulation within lysosomes, identifying another advantage conferred by their architecture. Indeed, these advantageous cellular interactions enhanced the gene silencing potency of PEI-SNAs by 10-fold relative to polyplexes. Finally, cytocompatibility studies showed that PEI-SNAs exhibit decreased toxicity per PEI content relative to polyplexes, allowing the use of more polycation. Our studies provide critical insight into design considerations for engineering siRNA carriers and warrant future investigation of how nanocarrier architecture influences cellular-, organ-, and organism-level interactions.

Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Keywords: RNA interference; gene regulation; nanoparticle; polycation; polyethylenimine; polyplex; siRNA; spherical nucleic acid

References

  1. Proc Natl Acad Sci U S A. 2014 Jul 8;111(27):9739-44 - PubMed
  2. Bioconjug Chem. 2008 Jul;19(7):1448-55 - PubMed
  3. Nano Lett. 2009 May;9(5):2059-64 - PubMed
  4. Nat Rev Genet. 2015 Sep;16(9):543-52 - PubMed
  5. Nano Lett. 2009 Jun;9(6):2402-6 - PubMed
  6. Nat Nanotechnol. 2018 Jan;13(1):82-89 - PubMed
  7. Pharm Res. 2006 Aug;23(8):1868-76 - PubMed
  8. ACS Nano. 2012 Nov 27;6(11):9447-54 - PubMed
  9. Cancer Res. 2007 Jun 15;67(12):5957-64 - PubMed
  10. Angew Chem Int Ed Engl. 2015 Jan 7;54(2):527-31 - PubMed
  11. Nano Lett. 2009 Jan;9(1):308-11 - PubMed
  12. Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11613-8 - PubMed
  13. Nat Biotechnol. 2015 Aug;33(8):870-6 - PubMed
  14. J Neurooncol. 2011 Aug;104(1):55-63 - PubMed
  15. Nanomedicine (Lond). 2012 Aug;7(8):1133-48 - PubMed
  16. J Am Chem Soc. 2014 May 28;136(21):7726-33 - PubMed
  17. PLoS One. 2015 Apr 09;10(4):e0122581 - PubMed
  18. Eur J Pharm Sci. 2012 Mar 12;45(4):459-66 - PubMed
  19. Biomacromolecules. 2012 Jan 9;13(1):73-83 - PubMed
  20. Sci Transl Med. 2013 Oct 30;5(209):209ra152 - PubMed
  21. Nat Rev Drug Discov. 2009 Feb;8(2):129-38 - PubMed
  22. Biochim Biophys Acta. 2014 Dec;1838(12):3097-106 - PubMed
  23. Nat Rev Cancer. 2017 Jan;17(1):20-37 - PubMed
  24. Nat Biotechnol. 2013 Jul;31(7):638-46 - PubMed
  25. Mol Ther. 2013 Jan;21(1):149-57 - PubMed
  26. Nat Methods. 2012 Jun 28;9(7):676-82 - PubMed
  27. Bioconjug Chem. 2016 Sep 21;27(9):2124-31 - PubMed
  28. ACS Nano. 2012 Aug 28;6(8):7340-51 - PubMed
  29. Nat Rev Genet. 2014 Aug;15(8):541-55 - PubMed
  30. Nanomedicine (Lond). 2016 Jan;11(1):81-100 - PubMed
  31. Macromol Biosci. 2015 May;15(5):622-35 - PubMed
  32. Eur J Pharm Biopharm. 2011 Nov;79(3):473-84 - PubMed
  33. Adv Genet. 2014;88:263-88 - PubMed
  34. Methods Mol Biol. 2017;1570:1-15 - PubMed
  35. Bioconjug Chem. 2010 Dec 15;21(12):2250-6 - PubMed
  36. Nano Lett. 2007 Dec;7(12):3818-21 - PubMed
  37. Nano Lett. 2007 Jun;7(6):1542-50 - PubMed
  38. Mol Ther. 2017 Jul 5;25(7):1476-1490 - PubMed
  39. Nanomedicine. 2010 Apr;6(2):344-54 - PubMed
  40. Biomacromolecules. 2016 Jan 11;17(1):200-7 - PubMed
  41. J Am Chem Soc. 2009 Feb 18;131(6):2072-3 - PubMed
  42. Small. 2015 Feb 25;11(8):952-62 - PubMed
  43. Genes Dev. 2015 Apr 1;29(7):732-45 - PubMed
  44. J Am Chem Soc. 2011 Jun 22;133(24):9254-7 - PubMed
  45. ACS Nano. 2014 Sep 23;8(9):8979-91 - PubMed
  46. Nano Lett. 2012 Jul 11;12(7):3867-71 - PubMed
  47. Nanoscale. 2012 Aug 21;4(16):5102-9 - PubMed
  48. Annu Rev Biomed Eng. 2012;14:1-16 - PubMed
  49. Mol Ther. 2011 Jan;19(1):103-12 - PubMed
  50. Nano Lett. 2010 Jul 14;10(7):2543-8 - PubMed
  51. J Drug Target. 2013 Aug;21(7):684-92 - PubMed

Publication Types

Grant support