Hyaluronic acid-polyethyleneimine conjugate for target specific intracellular delivery of siRNA

被引:127
作者
Jiang, Ge [1 ,2 ,3 ]
Park, Kitae [4 ]
Kim, Jiseok [1 ]
Kim, Ki Su [1 ]
Oh, Eun Ju [1 ]
Kang, Hyungu
Han, Su-Eun [5 ]
Oh, Yu-Kyoung [5 ]
Park, Tae Gwan [6 ]
Hahn, Sei Kwang [1 ,4 ]
机构
[1] Pohang Univ Sci & Technol, Dept Mat Sci & Engn, Pohang 790784, South Korea
[2] Dalian Univ Technol, Bioengn Coll, Dalian 116622, Liaoning, Peoples R China
[3] Dalian Univ Technol, Key Lab Bioorgan Chem, Dalian 116622, Liaoning, Peoples R China
[4] POSTECH I Bio Program, Pohang 790784, South Korea
[5] Korea Univ, Sch Life Sci & Biotechnol, Seoul 136701, South Korea
[6] Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea
关键词
hyaluronic acid; polyethyleneimine; small interfering RNA; LYVE-1 HA receptor; intracellular gene delivery;
D O I
10.1002/bip.20978
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A novel target specific small interfering RNA (siRNA) delivery system was successfully developed using I polyethyleneimine (PEI)-hyaluronic acid (HA) conjugate. Anti-PGL3-Luc siRNA was used as a model system suppressing the PGL3-Luc gene expression. The siRNA/PEI-HA complex with an average size of ca.21 nm appeared to be formed by electrostatic interaction between the negatively charged siRNA and the positively charged PEI of PEI-HA conjugate. The cytotoxicity of siRNA/PEI-HA complex to B16F1 cells was lower than that of siRNA/PEI complex according to the MTTassay. When B16F1 and HEK-293 cells were treated with fluorescein isothiocyanate (FITC) labeled siRNA/PEI-HA complex, B16F1 cells, with a lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), showed higher green fluorescent intensity than HEK-293 cells because of the HA receptor mediated endocytosis of the complex. Accordingly, the PGL3-Luc gene silencing of anti-PGL3-Luc siRNA/PEI-HA complex was more efficient in B16F1 cells than in HEK-293 cells. In addition, the inhibited PGL3-Luc gene silencing effect in the presence of free HA in the transfection medium revealed that siRNA/HA-PEI complex was selectively taken up to B16F1 cells via HA receptor mediated endocytosis. All these results demonstrated that the intracellular delivery of anti-PGL3-Luc siRNA/PEI-HA complex could be facilitated by the HA receptor mediated endocytosis. (c) 2008 Wiley Periodicals, Inc.
引用
收藏
页码:635 / 642
页数:8
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