Crosslinked linear polyethylenimine enhances delivery of DNA to the cytoplasm
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Hammond_Crosslinked linear.pdf
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Author(s)
Bonner, Daniel K.
Zhao, Xiaoyong
Buss, Hilda
Langer, Robert S
Hammond, Paula T
Date Issued
September 2012
Journal
Journal of Controlled Release
Publisher
Elsevier
Citation
Bonner, Daniel K., Xiaoyong Zhao, Hilda Buss, Robert Langer, and Paula T. Hammond. “Crosslinked Linear Polyethylenimine Enhances Delivery of DNA to the Cytoplasm.” Journal of Controlled Release 167, no. 1 (April 2013): 101–7.
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Author's final manuscript
Abstract
Crosslinked polyethylenimines (PEIs) have been frequently examined over the past decade since they can maintain the transfection efficiency of commercially available, 25 k branched PEI, but exhibit less cytotoxicity. The argument is often made that the degradability of such polymers, generally synthesized with either disulfide or hydrolytically degradable crosslinkers, is critical to the high efficiency and low toxicity of the system. In this work, we present a crosslinked linear PEI (xLPEI) system in which either disulfide-responsive or non-degradable linkages are incorporated. As with previous systems, strong transfection efficiency in comparison with commercial standards was achieved with low cytotoxicity. However, these properties were shown to be present when either the degradable or non-degradable crosslinker was used. Uncomplexed polymer was demonstrated to be the critical factor determining transfection efficiency for these polymers, mediating efficient endosomal escape without signs of cell membrane damage. While several crosslinked PEI systems in the literature have demonstrated the effect of the disulfide moiety, this work demonstrates that disulfide-mediated unpackaging may not be as important as conventionally thought for some PEI systems.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.jconrel.2012.09.004
