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Reducible Hyaluronic Acid–siRNA Conjugate for Target Specific Gene Silencing

Despite wide applications of polymer–drug conjugates, there are only a few polymer–siRNA conjugates like poly(ethylene glycol) conjugated siRNA. In this work, reducible hyaluronic acid (HA)–siRNA conjugate was successfully developed for target specific systemic delivery of siRNA to the liver. The conjugation of siRNA to HA made it possible to form a compact nanocomplex of siRNA with relatively nontoxic linear polyethyleneimine (LPEI). After characterization of HA–siRNA conjugate by size exclusion chromatography (SEC) and gel electrophoresis, its complex formation with LPEI was investigated with a particle analyzer. The HA–siRNA/LPEI complex had a mean particle size of ca. 250 nm and a negative or neutral surface charge at physiological condition. The reducible HA–siRNA/LPEI complex showed a higher in vitro gene silencing efficiency than noncleavable HA–siRNA/LPEI complex. Furthermore, after systemic delivery, apolipoprotein B (ApoB) specific HA–siApoB/LPEI complex was target specifically delivered to the ...

Authors:   Kitae Park; Jeong-A Yang; Min-Young Lee; Hwiwon Lee; Sei Kwang Hahn
Journal:   Bioconjugate Chemistry
Year:   2013
DOI:   10.1021/bc4001257
Publication date:   17-Jun-2013
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