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, Kwang Meyung Kim, Ick Chan Kwon, Jun Young Lee, Doo Sung Lee, Jae Chan Park, Jae Hyung Park

Research output: Contribution to journalArticle

49 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 Nov 13
Externally publishedYes

Fingerprint

Hyaluronic Acid
Small Interfering RNA
Neoplasms
Methacrylates
Gene Silencing
Disulfides
Cytosol
Melanoma
Fibroblasts

Keywords

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

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Yoon, H. Y., Kim, H. R., Saravanakumar, G., Heo, R., Chae, S. Y., Um, W., ... 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

Bioreducible hyaluronic acid conjugates as siRNA carrier for tumor targeting. / Yoon, Hong Yeol; Kim, Hyun Ryoung; Saravanakumar, Gurusamy; Heo, Roun; Chae, Su Young; Um, Wooram; Kim, Kwang Meyung; Kwon, Ick Chan; Lee, Jun Young; Lee, Doo Sung; Park, Jae Chan; Park, Jae Hyung.

In: Journal of Controlled Release, Vol. 172, No. 3, 13.11.2013, p. 653-661.

Research output: Contribution to journalArticle

Yoon, HY, Kim, HR, Saravanakumar, G, Heo, R, Chae, SY, Um, W, Kim, KM, Kwon, IC, Lee, JY, Lee, DS, Park, JC & Park, JH 2013, 'Bioreducible hyaluronic acid conjugates as siRNA carrier for tumor targeting', Journal of Controlled Release, vol. 172, no. 3, pp. 653-661. https://doi.org/10.1016/j.jconrel.2013.09.008
Yoon, Hong Yeol ; Kim, Hyun Ryoung ; Saravanakumar, Gurusamy ; Heo, Roun ; Chae, Su Young ; Um, Wooram ; Kim, Kwang Meyung ; Kwon, Ick Chan ; Lee, Jun Young ; Lee, Doo Sung ; Park, Jae Chan ; Park, Jae Hyung. / Bioreducible hyaluronic acid conjugates as siRNA carrier for tumor targeting. In: Journal of Controlled Release. 2013 ; Vol. 172, No. 3. pp. 653-661.
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AU - Kwon, Ick Chan

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