Hyaluronic acid–siRNA conjugates complexed with cationic solid lipid nanoparticles for target specific gene silencing
SCIE
SCOPUS
- Title
- Hyaluronic acid–siRNA conjugates complexed with cationic solid lipid nanoparticles for target specific gene silencing
- Authors
- Lee, MY; Kong, WH; Jung, HS; Hahn, SK
- Date Issued
- 2014-04
- Publisher
- ROYAL SOC CHEMISTRY
- Abstract
- Despite extensive investigations on siRNA delivery systems for the past decade, there has been no clinically available product until now. In this work, reducible hyaluronic acid (HA)-siRNA conjugate was successfully synthesized and used to make a complex with cationic solid lipid nanoparticles (CSLNs) for the development of a liver specific siRNA delivery system. The reducible HA-siRNA conjugate was synthesized by the disulfide-thiol exchange reaction between pyridyldithiol modified HA and thiolated siRNA. The remaining pyridyldithiol was further blocked with cysteine. The biomimetic CSLNs were prepared by reconstituting the composition of natural apolipoprotein-free low density lipoproteins (LDLs). The formation of the HA-siRNA/CSLN complex was confirmed by gel electrophoresis (GE), dynamic light scattering (DLS), and atomic force microscopy (AFM). The HA-siRNA/CSLN complex showed remarkably low cytotoxicity and high transfection efficiency in the presence of serum. The therapeutic index (LC50/IC50) of the HAsiRNA/ CSLN complex was statistically much higher than that of a HA-siRNA conjugate or siRNA complexed with commercially available siRNA transfection reagents like in vivo jetPEI and INTERFERin, as well as an siRNA/CSLN complex. The HA-siRNA/CSLN complex can be effectively applied as a model system for the treatment of liver diseases, such as liver fibrosis and liver cancer.
- Keywords
- IN-VIVO DELIVERY; CELLULAR UPTAKE; LIVER; CELLS; LUNG; RNA
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/13751
- DOI
- 10.1039/C4RA01485E
- ISSN
- 2046-2069
- Article Type
- Article
- Citation
- RSC Advances, vol. 4, no. 37, page. 19338 - 19344, 2014-04
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