Journal
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
Volume 93A, Issue 2, Pages 585-594Publisher
WILEY
DOI: 10.1002/jbm.a.32525
Keywords
PAMAM dendrimer; gliomas; targeting; gene delivery; antisense oligonucleotides
Funding
- China National Natural Scientific Foundation [50573056, 30772231]
- Tianjin Science and Technology Committee [05YFJZJC1002, 06YFSZSF01100, 07ZCGHHZ1000]
- Program for New Century Excellent Talents in University [NCET-07-0615]
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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
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