Cationic derivatives of biocompatible hyaluronic acids for delivery of siRNA and antisense oligonucleotides.
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.
Han
Su-Eun
SE
School of Life Sciences and Biotechnology, Korea University, Seoul, South Korea.
Kang
Hyungu
H
Shim
Ga Yong
GY
Kim
Sun Jae
SJ
Choi
Han-Gon
HG
Kim
Jiseok
J
Hahn
Sei Kwang
SK
Oh
Yu-Kyoung
YK
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
D002412:Cations; D004337:Drug Carriers; D016376:Oligonucleotides, Antisense; D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins; D011094:Polyethyleneimine; D006820:Hyaluronic Acid