Bioreducible hyaluronic acid conjugates as siRNA carrier for tumor targeting

Hong Yeol Yoon, Hyun Ryoung Kim, Gurusamy Saravanakumar, Roun Heo, Su Young Chae, Wooram Um, Kwangmeyung Kim, Ick Chan Kwon, Jun Young Lee, Doo Sung Lee, Jae Chan Park, Jae Hyung Park

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54 Citations (Scopus)

Abstract

The successful clinical translation of siRNA-based therapeutics requires efficient carrier systems that can specifically deliver siRNA within the cytosol of the target cells. Although numerous polymeric nanocarriers forming ionic complexes with siRNA have been investigated for cancer therapy, their poor stability and lack of tumor targetability have impeded their in vivo applications. To surmount these limitations, we synthesized a novel type of biodegradable hyaluronic acid-graft-poly(dimethylaminoethyl methacrylate) (HPD) conjugate that can form complexes with siRNA and be chemically crosslinked via the formation of the disulfide bonds under facile conditions. The crosslinked siRNA-HPD (C-siRNA-HPD) complexes exhibited high stability in a 50% serum solution, as compared to the uncrosslinked siRNA-HPD (U-siRNA-HPD) complexes and free siRNA. Both the C-siRNA-HPD and U-siRNA-HPD complexes were efficiently taken up by the CD44-overexpressing melanoma cells (B16F10), but not by the normal fibroblast cells (NIH3T3). When the RFP-expressing B16F10 cells were treated with the complexes or free siRNA, the C-siRNA-HPD complexes showed the highest decrease in RFP expression. In vivo studies demonstrated the selective accumulation of C-siRNA-HPD complexes at the tumor site after their systemic administration into tumor-bearing mice, resulting in an efficient gene silencing effect. Overall, these results suggest that the HPD conjugate could be used as an efficient carrier for the tumor-targeted delivery of siRNA.

Original languageEnglish
Pages (from-to)653-661
Number of pages9
JournalJournal of Controlled Release
Volume172
Issue number3
DOIs
Publication statusPublished - 2013

Keywords

  • Bioreducible conjugate
  • Hyaluronic acid
  • Stability
  • Tumor targetability
  • siRNA

ASJC Scopus subject areas

  • Pharmaceutical Science

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  • Cite this

    Yoon, H. Y., Kim, H. R., Saravanakumar, G., Heo, R., Chae, S. Y., Um, W., Kim, K., Kwon, I. C., Lee, J. Y., Lee, D. S., Park, J. C., & Park, J. H. (2013). Bioreducible hyaluronic acid conjugates as siRNA carrier for tumor targeting. Journal of Controlled Release, 172(3), 653-661. https://doi.org/10.1016/j.jconrel.2013.09.008