Format

Send to

Choose Destination
Mol Pharm. 2009 Sep-Oct;6(5):1612-9. doi: 10.1021/mp9000958.

Polymer-enhanced adenoviral transduction of CAR-negative bladder cancer cells.

Author information

1
Department of Microbiology, Medical University of South Carolina, Charleston, South Carolina, USA.

Abstract

The application of adenoviral gene therapy for cancer is limited by immune clearance of the virus as well as poor transduction efficiency, since the protein used for viral entry (CAR) serves physiological functions in adhesion and is frequently decreased among cancer cells. Cationic polymers have been used to enhance adenoviral gene delivery, but novel polymers with low toxicity are needed to realize this approach. We recently identified polymers that were characterized by high transfection efficiency of plasmid DNA and a low toxicity profile. In this study we evaluated the novel cationic polymer EGDE-3,3' for its potential to increase adenoviral transduction of the CAR-negative bladder cancer cell line TCCSUP. The amount of adenovirus required to transduce 50-60% of the cells was reduced 100-fold when Ad.GFP was preincubated with the EGDE-3,3' polymer. Polyethyleneimine (pEI), a positively charged polymer currently used as a standard for enhancing adenoviral transduction, also increased infectivity, but transgene expression was consistently higher with EGDE-3,3'. In addition, EGDE-3,3'-supplemented transduction of an adenovirus expressing an apoptosis inducing transgene, Ad.GFP-TRAIL, significantly enhanced the amount of cell death. Thus, our results indicate that novel biocompatible polymers may be useful in improving the delivery of adenoviral gene therapy.

PMID:
19655763
PMCID:
PMC2757475
DOI:
10.1021/mp9000958
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for American Chemical Society Icon for PubMed Central
Loading ...
Support Center