The DOI matches its Crossref record.
Influence of Polyethylene Glycol Chain Length on the Physicochemical and Biological Properties of Poly(ethylene imine)-graft-Poly(ethylene glycol) Block Copolymer/SiRNA Polyplexes
Abstract
Polyplexes between siRNA and poly(ethylene imine) (PEI) derivatives are promising nonviral carriers for siRNA. The polyplex stability is of critical importance for efficient siRNA delivery to the cytoplasm. Here, we investigate the effect of PEGylation at a constant ratio ( approximately 50%) on the biophysical properties of the polyplexes. Particle size, zeta potential, and stability against heparin as well as RNase digestion and reporter gene knockdown under in vitro conditions of different siRNA polyplexes were characterized. Stability and size of siRNA polyplexes were clearly influenced by PEI-PEG structure, and high degrees of substitution such as PEI(25k)-g-PEG(550)(30) resulted in large (300-400 nm), diffuse complexes (AFM) which showed condensation behavior only at high N/P ratios. All other polyplexes and the PEI control showed similar sizes (150 nm) and compact structures in AFM, with complete condensation reached at N/P ratio of 3. Stability of siRNA polyplexes against heparin displacement and RNase digestion could be modified by PEGylation. Protection against RNase digestion was highest for PEI(25k)-g-PEG(5k)(4) and PEI(25k)-g-PEG(20k)(1), while siRNA/PEI provided insufficient protection. In knockdown experiments using NIH/3T3 fibroblasts stably expressing beta-galactosidase, it was shown that PEG chain length had a significant influence on biological activity of siRNA. Polyplexes with siRNA containing PEI(25k)-g-PEG(5k)(4) and PEI(25k)-g-PEG(20k)(1) yielded similar efficiencies of ca. 70% knockdown as lipofectamine controls. Confocal microscopy demonstrated enhanced cellular uptake of siRNA into cytosol by polyplexes formation with PEI copolymers. In conclusion, both the chain length and graft density of PEG were found to strongly influence siRNA condensation and stability and hence affect the knockdown efficiency of PEI-PEG/siRNA polyplexes.
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Citations
Cited by
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Beck-Broichsitter, M., Merkel, O. M., & Kissel, T. (2012) · Journal of Controlled Release · doi:10.1016/j.jconrel.2011.12.004 · Cited by 200
Self-citationShen, H., Hong, S., Prud’homme, R. K., & Liu, Y. (2011) · Journal of Nanoparticle Research · doi:10.1007/s11051-011-0354-7 · Cited by 120
Gary, D. J., Min, J., Kim, Y., Park, K., & Won, Y. (2013) · Macromolecular Bioscience · doi:10.1002/mabi.201300046 · Cited by 80
Zhang, Y., Zheng, M., Kissel, T., & Agarwal, S. (2012) · Biomacromolecules · doi:10.1021/bm2015174 · Cited by 60
Self-citationZhou, L., Chen, Z., Chi, W., Yang, X., Wang, W., & Zhang, B. (2012) · Biomaterials · doi:10.1016/j.biomaterials.2011.11.060 · Cited by 54
Polymeric micelles for siRNA delivery
Falamarzian, A., Xiong, X.-B., Uludag, H., & Lavasanifar, A. (2012) · Journal of Drug Delivery Science and Technology · doi:10.1016/s1773-2247(12)50004-3 · Cited by 25
Metadata
- Authors
- Mao, S., Neu, M., Germershaus, O., Merkel, O., Sitterberg, J., Bakowsky, U., & Kissel, T.
- Venue
- Bioconjugate Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2006-09-01
- Volume
- 17
- Issue
- 5
- Pages
- 1209-1218
- ISSN
- 1043-1802 (ISSN-L)
- 1520-4812
- OpenAlex
- W2078377919
- Cited by
- 319
- References
- 0
- FWCI
- 7.98
- Type
- journal article
- Language
- en
- Open access
- closed
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