Journal
BIOMACROMOLECULES
Volume 12, Issue 10, Pages 3592-3600Publisher
AMER CHEMICAL SOC
DOI: 10.1021/bm200807s
Keywords
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Funding
- NCI NIH HHS [T32 CA153952, T32 CA130840] Funding Source: Medline
- NIGMS NIH HHS [T32 GM007309] Funding Source: Medline
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A new 320-member polymer library of end-modified poly(beta-amino ester)s was synthesized. This library was chosen such that small differences to the structures of component backbone, side-chain, and end-group monomers could be systematically and simultaneously evaluated. The in vitro transfection efficacy and cytotoxicity of DNA nanoparticles formed from this library were assessed. This library approach not only enabled us to synthesize and test a large variety of structures rapidly but also provided us with a robust data set to analyze for the effect of small structural permutations to polymer chain structure. Small changes to the side chains, backbones, and end groups within this polymer library produced dramatic results, with transfection efficacy of CMV-Luc varying over 4 orders in a 96-well plate format. Increasing hydrophobicity of the base polymer backbone and side chair. tended to increase transfection efficacy, but the most hydrophobic side chains and backbones showed the least requirement for a hydrophobic pair. Optimal PBAE formulations were superior to commercially available nonviral alternatives FuGENE HD and Lipofectamine 2000, enabling similar to 3-fold increased luminescence (2.2 x 10(6) RLU/well vs 8.1 x 10(5) RLU/well) and 2-fold increased transfection percentage (76.7% vs 42.9%) as measured by flow cytometry with comparable or reduced toxicity.
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