Hyaluronic acid complexed to biodegradable poly L-arginine for targeted delivery of siRNAs

Eun Joong Kim, Gayong Shim, Kwangmyeung Kim, Ick Chan Kwon, Yu Kyoung Oh, Chang Koo Shim

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Background: Small interfering RNA (siRNA) has been recognized as a new therapeutic drug to treat various diseases by inhibition of oncogene or viral gene expression. Because hyaluronic acid (HA) has been described as a biocompatible biomaterial, we tested the nanoparticles formed by electrostatic complexation of negatively-charged HA and cationic poly L-arginine (PLR) for siRNA delivery systems. Methods: Different electrostatic complexes of HA and PLR (HPs) were formulated: HP101 with 50% (w/w) HA and HP110 with 9% (w/w) HA. Results: Gel retardation assays showed that HP101 and HP110 could form complexes with siRNAs. The diameters of these complexes were less than 200 nm. Cellular delivery efficiency of siRNAs by HPs depended on cell surface CD44 density. The HP-mediated delivery of siRNAs was highest in WM266.4 cells followed by B16F10 cells and COS-7 cells, in parallel with CD44 surface densities of these cell lines. TC50 values (i.e. the HP concentrations at which 50% of cells were viable after treatment) were used as indicators of cytotoxicity. HP101 showed TC50 values that were 2-fold and 23-fold higher than those of HP110 and PLR, respectively. After delivery into cells, siRNA exerted target-specific RNA interference effects on mRNA and protein levels. Three days after treatment of red fluorescent protein (RFP)-expressing B16F10 cells with RFP-specific siRNA complexed to HP101, cellular fluorescence signals were reduced. Intratumoral administration of RFP-specific siRNA via HP101 delivery significantly reduced the expression of RFP in tumor tissues. Conclusions: HP101 may function as a biocompatible polymeric carrier of siRNAs and have possible application to localized siRNA delivery in vivo.

Original languageEnglish
Pages (from-to)791-803
Number of pages13
JournalJournal of Gene Medicine
Volume11
Issue number9
DOIs
Publication statusPublished - 2009 Oct 2
Externally publishedYes

Fingerprint

Hyaluronic Acid
Small Interfering RNA
Static Electricity
Viral Genes
COS Cells
Biocompatible Materials
Electrophoretic Mobility Shift Assay
RNA Interference
Oncogenes
Nanoparticles
polyarginine
Fluorescence
Gene Expression
Cell Line
Messenger RNA
red fluorescent protein
Pharmaceutical Preparations
Neoplasms
Proteins

Keywords

  • Biodegradable cationic polymer
  • Hyaluronic acid
  • Poly L-arginine
  • siRNA delivery

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Genetics(clinical)
  • Drug Discovery

Cite this

Hyaluronic acid complexed to biodegradable poly L-arginine for targeted delivery of siRNAs. / Kim, Eun Joong; Shim, Gayong; Kim, Kwangmyeung; Kwon, Ick Chan; Oh, Yu Kyoung; Shim, Chang Koo.

In: Journal of Gene Medicine, Vol. 11, No. 9, 02.10.2009, p. 791-803.

Research output: Contribution to journalArticle

Kim, Eun Joong ; Shim, Gayong ; Kim, Kwangmyeung ; Kwon, Ick Chan ; Oh, Yu Kyoung ; Shim, Chang Koo. / Hyaluronic acid complexed to biodegradable poly L-arginine for targeted delivery of siRNAs. In: Journal of Gene Medicine. 2009 ; Vol. 11, No. 9. pp. 791-803.
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AU - Oh, Yu Kyoung

AU - Shim, Chang Koo

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