Cationic derivatives of biocompatible hyaluronic acids for delivery of siRNA and antisense oligonucleotides
- Authors
- Han, Su-Eun; Kang, Hyungu; Shim, Ga Yong; Kim, Sun Jae; Choi, Han-Gon; Kim, Jiseok; Hahn, Sei Kwang; Oh, Yu-Kyoung
- Issue Date
- Feb-2009
- Publisher
- TAYLOR & FRANCIS LTD
- Keywords
- Hyaluronic acid; cationic polymer; siRNA delivery; antisense oligonucleotides
- Citation
- JOURNAL OF DRUG TARGETING, v.17, no.2, pp.123 - 132
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF DRUG TARGETING
- Volume
- 17
- Number
- 2
- Start Page
- 123
- End Page
- 132
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/120684
- DOI
- 10.1080/10611860802472461
- ISSN
- 1061-186X
- 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 63139 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.
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