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Biocleavable Polyrotaxane−Plasmid DNA Polyplex for Enhanced Gene Delivery
Abstract
A biocleavable polyrotaxane, having a necklace-like structure consisting of many cationic alpha-cyclodextrins (alpha-CDs) and a disulfide-introduced poly(ethylene glycol) (PEG), was synthesized and examined as a nonviral gene carrier. The polyrotaxane formed a stable polyplex having positively charged surface even at low charge ratio. This is likely to be due to structural factors of the polyrotaxane, such as the mobile motion of alpha-CDs in the necklace-like structure. Rapid endosomal escape was observed 90 min after transfection. The positively charged surface and the good buffering capacity are advantageous to show the proton sponge effect. The pDNA decondensation occurred through disulfide cleavage of the polyrotaxane and subsequent supramolecular dissociation of the noncovalent linkages between alpha-CDs and PEG. Transfection of the DMAE-SS-PRX polyplex is independent of the amount of free polycation. Those properties played a key role for delivery of pDNA clusters to the nucleus. Therefore, the polyplex nature and the supramolecular dissociation of the polyrotaxane contributed to the enhanced gene delivery.
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Cited by
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Zhang, J., & Ma, P. X. (2013) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2013.05.001 · Cited by 836
Li, J., & Loh, X. J. (2008) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2008.02.011 · Cited by 787
Extracellularly Activated Nanocarriers: A New Paradigm of Tumor Targeted Drug Delivery
Gullotti, E., & Yeo, Y. (2009) · Molecular Pharmaceutics · doi:10.1021/mp900090z · Cited by 473
Rai, R., Alwani, S., & Badea, I. (2019) · Polymers · doi:10.3390/polym11040745 · Cited by 350
Material properties and applications of mechanically interlocked polymers
Hart, L. F., Hertzog, J. E., Rauscher, P. M., Rawe, B. W., Tranquilli, M. M., & Rowan, S. J. (2021) · Nature Reviews Materials · doi:10.1038/s41578-021-00278-z · Cited by 336
Metadata
- Authors
- Ooya, T., Choi, H. S., Yamashita, A., Yui, N., Sugaya, Y., Kano, A., Maruyama, A., Akita, H., Ito, R., Kogure, K., & Harashima, H.
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2006-03-01
- Volume
- 128
- Issue
- 12
- Pages
- 3852-3853
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- OpenAlex
- W2000835830
- Cited by
- 270
- References
- 0
- FWCI
- 7.98
- Type
- journal article
- Language
- en
- Open access
- closed
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- Ooya, T., Choi, H. S., Yamashita, A., Yui, N., Sugaya, Y., Kano, A., Maruyama, A., Akita, H., Ito, R., Kogure, K., & Harashima, H. (2006). Biocleavable Polyrotaxane−Plasmid DNA Polyplex for Enhanced Gene Delivery. Journal of the American Chemical Society. https://doi.org/10.1021/ja055868%2B
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