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A pH-Sensitive Polymer That Enhances Cationic Lipid-Mediated Gene Transfer
Abstract
The efficient release of nonviral gene carriers from endosomes is an important step for the successful delivery of DNA into the cell nucleus. A synthetic pH-sensitive anionic polymer, poly(propylacrylic acid) (PPAA), was designed to aid in endosomal escape of nonviral vectors and improve the transfection efficiencies with these vectors. Transfection of NIH3T3 fibroblasts with ternary physical mixtures of the cationic lipid DOTAP, pCMVbeta plasmid DNA, and PPAA showed marked enhancement of both gene expression levels and fraction of cells transfected compared to binary control mixtures of DOTAP and DNA. PPAA also significantly improved the serum-stability of DOTAP/DNA vectors. The DOTAP/DNA/PPAA vectors maintained high levels of transfection in media containing up to 50% serum. The striking enhancement of transfection efficiency with cationic lipid/DNA/PPAA mixtures, along with the enhanced serum-stability, suggests that PPAA may provide significant improvements for the in vivo intracellular delivery of drugs such as DNA, oligonucleotides, proteins, and peptides.
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Citations
Cited by
Design and development of polymers for gene delivery
Pack, D. W., Hoffman, A. S., Pun, S., & Stayton, P. S. (2005) · Nature Reviews Drug Discovery · doi:10.1038/nrd1775 · Cited by 2,568
Self-citationStimuli-reponsive polymers and their bioconjugates
GIL, E., & HUDSON, S. (2004) · Progress in Polymer Science · doi:10.1016/j.progpolymsci.2004.08.003 · Cited by 2,385
Endosomal escape pathways for delivery of biologicals
Varkouhi, A. K., Scholte, M., Storm, G., & Haisma, H. J. (2011) · Journal of Controlled Release · doi:10.1016/j.jconrel.2010.11.004 · Cited by 1,561
Cho, E. C., Xie, J., Wurm, P. A., & Xia, Y. (2009) · Nano Letters · doi:10.1021/nl803487r · Cited by 819
Multifunctional and stimuli-sensitive pharmaceutical nanocarriers
Torchilin, V. (2009) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2008.09.026 · Cited by 583
Metadata
- Authors
- Cheung, C. Y., Murthy, N., Stayton, P. S., & Hoffman, A. S.
- Venue
- Bioconjugate Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2001-10-27
- Volume
- 12
- Issue
- 6
- Pages
- 906-910
- ISSN
- 1043-1802 (ISSN-L)
- 1520-4812
- OpenAlex
- W2021741932
- Cited by
- 164
- References
- 0
- FWCI
- 2.50
- Type
- journal article
- Language
- en
- Open access
- closed
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- Cheung, C. Y., Murthy, N., Stayton, P. S., & Hoffman, A. S. (2001). A pH-Sensitive Polymer That Enhances Cationic Lipid-Mediated Gene Transfer. Bioconjugate Chemistry. https://doi.org/10.1021/bc0100408
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