Journal
BIOMATERIALS
Volume 32, Issue 23, Pages 5402-5410Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2011.04.016
Keywords
Drug delivery; Gene therapy; Nanoparticle; Stem cell; DNA; Cancer
Funding
- Institute for NanoBioTechnology at Johns Hopkins University
- TEDCO MSCRF [2009-MSCRFE-0098-00]
- National Institutes of Health [R01NS070024]
- Howard Hughes Medical Institute
- Robert Wood Johnson Foundation
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Glioblastoma (GB) is currently characterized by low survival rates and therapies with insufficient efficacy. Here, we describe biodegradable polymers that can deliver genes to primary GB cells as well as GB tumor stem cells in vitro with low non-specific toxicity and transfection efficiencies of up to 60.6 +/- 5% in normal (10%) serum conditions. We developed polymer-DNA nanoparticles that remained more stable in normal serum and could also be stored for at least 3 months in ready-to-use form with no measurable decrease in efficacy, expanding their potential in a practical or clinical setting. A subset of polymers was identified that shows a high degree of specificity to tumor cells compared with healthy astrocytes and human neural stem cells when cultured (separately or in co-culture), yielding higher transfection in GB cells while having little to no apparent effect on healthy cells. (C) 2011 Elsevier Ltd. All rights reserved.
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