Design of a multicomponent peptide-woven nanocomplex for delivery of siRNA

Eunsung Jun, Soyoun Kim, Jong Ho Kim, Kiweon Cha, In Seop So, Hye Nam Son, Byung Heon Lee, Kwang Meyung Kim, Ick Chan Kwon, Sang Yoon Kim, In-San Kim

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

We developed and tested a multicomponent peptide-woven siRNA nanocomplex (PwSN) comprising different peptides designed for efficient cellular targeting, endosomal escape, and release of siRNA. To enhance tumor-specific cellular uptake, we connected an interleukin-4 receptor-targeting peptide (I4R) to a nine-arginine peptide (9r), yielding I4R-9r. To facilitate endosomal escape, we blended endosomolytic peptides into the I4R-9r to form a multicomponent nanocomplex. Lastly, we modified 9r peptides by varying the number and positions of positive charges to obtain efficient release of siRNA from the nanocomplex in the cytosol. Using this step-wise approach for overcoming the biological challenges of siRNA delivery, we obtained an optimized PwSN with significant biological activity in vitro and in vivo. Interestingly, surface plasmon resonance analyses and three-dimensional peptide models demonstrated that our designed peptide adopted a unique structure that was correlated with faster complex disassembly and a better gene-silencing effect. These studies further elucidate the siRNA nanocomplex delivery pathway and demonstrate the applicability of our stepwise strategy to the design of siRNA carriers capable of overcoming multiple challenges and achieving efficient delivery.

Original languageEnglish
Article numbere0118310
JournalPLoS One
Volume10
Issue number2
DOIs
Publication statusPublished - 2015 Feb 23
Externally publishedYes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Jun, E., Kim, S., Kim, J. H., Cha, K., So, I. S., Son, H. N., Lee, B. H., Kim, K. M., Kwon, I. C., Kim, S. Y., & Kim, I-S. (2015). Design of a multicomponent peptide-woven nanocomplex for delivery of siRNA. PLoS One, 10(2), [e0118310]. https://doi.org/10.1371/journal.pone.0118310