Evaluation of folate-PAMAM for the delivery of antisense oligonucleotides to rat C6 glioma cells in vitro and in vivo

被引:53
作者
Kang, Chunsheng [2 ,3 ]
Yuan, Xubo [1 ]
Li, Fei [1 ]
Pu, Peiyu [2 ,3 ]
Yu, Shizhu [4 ]
Shen, Changhong [3 ]
Zhang, Zhiyong [3 ]
Zhang, Yunting [5 ]
机构
[1] Tianjin Univ, Sch Mat Sci & Engn, Tianjin 300072, Peoples R China
[2] Tianjin Neurol Inst, Lab Neurooncol, Tianjin 300052, Peoples R China
[3] Tianjin Med Univ Gen Hosp, Dept Neurosurg, Tianjin 300052, Peoples R China
[4] Tianjin Med Univ Gen Hosp, Dept Neurol, Tianjin 300052, Peoples R China
[5] Tianjin Med Univ Gen Hosp, Dept Radiol, Tianjin 300052, Peoples R China
关键词
PAMAM dendrimer; gliomas; targeting; gene delivery; antisense oligonucleotides; GROWTH-FACTOR RECEPTOR; GENE DELIVERY; EGF RECEPTOR; POLYAMIDOAMINE DENDRIMER; CELLULAR DELIVERY; RNA; OLIGODEOXYNUCLEOTIDES; THERAPY; TISSUES; SYSTEM;
D O I
10.1002/jbm.a.32525
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
In the current study, we evaluated the efficiency of folate-polyamidoamine dendrimers conjugates (FA-PAMAM) for the in situ delivery of therapeutic antisense oligonucleotides (ASODN) that could inhibit the growth of C6 glioma cells. Folic acid was coupled to the surface amino groups of G5-PAMAM dendrimer (G5D) through a 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide bond, and ASODNs corresponding to rat epidermal growth factor receptor (EGFR) were then complexed with FA-PAMAM. At an ASODN to PAMAM ratio of 16:1, agarose electrophoresis indicated that antisense oligonucleotides were completely complexed with PAMAM or FA-PAMAM. The ASODN transfection rates mediated by FA-PAMAM and PAMAM were superior to oligofectamine, resulting in greater suppression of EGFR expression and glioma cell growth. Stereotactic injection of EGFR ASODN:FA-PAMAM complexes into established rat C6 intracranial gliomas resulted in greater suppression of tumor growth and longer survival time of tumor-bearing rats compared with PAMAM and oligofectamine-mediated EGFR-ASODN therapy. The current study demonstrates the suitability of folate-PAMAM dendrimer conjugates for efficient EGFR ASODN delivery into glioma cells, wherein they release the ASODN from the FA-PAMAM to knock down EGFR expression in C6 glioma cells, both in vitro and in vivo. FA-PAMAM may thus represent a novel delivery system for short oligonucleotides in glioma-targeted therapy. (C) 2009 Wiley Periodicals, Inc. J Biomed Mater Res 93A: 585-594, 2010
引用
收藏
页码:585 / 594
页数:10
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