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

✍ Scribed by Chunsheng Kang; Xubo Yuan; Fei Li; Peiyu Pu; Shizhu Yu; Changhong Shen; Zhiyong Zhang; Yunting Zhang

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 912 KB
• Volume: 9999A
• Category: Article
• ISSN: 1549-3296
• DOI: 10.1002/jbm.a.32525

✦ Synopsis

Abstract

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. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010