title: Cationic derivatives of biocompatible hyaluronic acids for delivery of siRNA and antisense oligonucleotides.
abstract: In this study, we tested the use of cationic polymer derivatives of biocompatible hyaluronic acid (HA) as a delivery system of siRNA and antisense oligonucleotides. HA was modified with cationic polymer polyethylenimine (PEI). When compared with PEI alone, cationic PEI derivatives of HA (HA-PEI) provided increased cellular delivery of Small interfering RNA (siRNA) in B16F1, A549, HeLa, and Hep3B tumor cells. Indeed, more than 95% of the cells were positive for siRNA following its delivery with HA-PEI. A survivin-specific siRNA that was delivered using HA-PEI potently reduced the mRNA expression levels of the target gene in all of the cell lines. By contrast, survivin-specific siRNA delivered by PEI alone did not induce a significant reduction in mRNA levels. In green fluorescent protein (GFP)-expressing 293 T cells, a loss of GFP expression was evident in the cells that had been treated with GFP-specific siRNA and HA-PEI complex. The inhibition of target gene expression by antisense oligonucleotide G3139 was also enhanced after delivery with HA-PEI. Moreover, HA-PEI displayed lower cytotoxicity than PEI alone. These results suggest that HA-PEI could be further developed as biocompatible delivery systems of siRNA and antisense oligonucleotides for enhanced cellular uptake and inhibition of target gene expression.
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Seoul, South Korea.
authors.forename: Su-Eun
authors.initials: SE
authors.lastname: Han
authors.forename: Hyungu
authors.initials: H
authors.lastname: Kang
authors.forename: Ga Yong
authors.initials: GY
authors.lastname: Shim
authors.forename: Sun Jae
authors.initials: SJ
authors.lastname: Kim
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
authors.forename: Jiseok
authors.initials: J
authors.lastname: Kim
authors.forename: Sei Kwang
authors.initials: SK
authors.lastname: Hahn
authors.forename: Yu-Kyoung
authors.initials: YK
authors.lastname: Oh
mesh_terms: D000818:Animals; D002412:Cations; D045744:Cell Line, Tumor; D004337:Drug Carriers; D049452:Green Fluorescent Proteins / Q000737:chemistry; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D011094:Polyethyleneimine / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D002412:Cations; D004337:Drug Carriers; D016376:Oligonucleotides, Antisense; D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins; D011094:Polyethyleneimine; D006820:Hyaluronic Acid