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Transferrin-Containing, Cyclodextrin Polymer-Based Particles for Tumor-Targeted Gene Delivery
Abstract
Transferrin is a well-studied ligand for tumor targeting due to upregulation of transferrin receptors in numerous cancer cell types. Here, we report the development of a transferrin-modified, cyclodextrin polymer-based gene delivery system. The delivery system is comprised of a nanoparticle (formed by condensation of a cyclodextrin polycation with nucleic acid) that is surface-modified to display poly(ethylene glycol) (PEG) for increasing stability in biological fluids and transferrin for targeting of cancer cells that express transferrin receptor. A transferrin-PEG-adamantane conjugate is synthesized for nanoparticle modification. The transferrin conjugate retains high receptor binding and self-assembles with the nanoparticles by adamantane (host) and particle surface cyclodextrin (guest) inclusion complex formation. At low transferrin modification, the particles remain stable in physiologic salt concentrations and transfect K562 leukemia cells with increased efficiency over untargeted particles. The increase in transfection is eliminated when transfections are conducted in the presence of excess free transferrin. The transferrin-modified nanoparticles are appropriate for use in the systemic delivery of nucleic acid therapeutics for metastatic cancer applications.
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Citations
Cited by
Non-viral vectors for gene-based therapy
Yin, H., Kanasty, R. L., Eltoukhy, A. A., Vegas, A. J., Dorkin, J. R., & Anderson, D. G. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3763 · Cited by 3,123
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-citationNonviral vectors for gene delivery
Mintzer, M. A., & Simanek, E. E. (2009) · Chemical Reviews · doi:10.1021/cr800409e · Cited by 2,366
Delivery materials for siRNA therapeutics
Kanasty, R., Dorkin, J. R., Vegas, A., & Anderson, D. (2013) · Nature Materials · doi:10.1038/nmat3765 · Cited by 1,800
Nicolas, J., Mura, S., Brambilla, D., Mackiewicz, N., & Couvreur, P. (2013) · Chem. Soc. Rev. · doi:10.1039/c2cs35265f · Cited by 1,270
Metadata
- Authors
- Bellocq, N. C., Pun, S. H., Jensen, G. S., & Davis, M. E.
- Venue
- Bioconjugate Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2003-11-01
- Volume
- 14
- Issue
- 6
- Pages
- 1122-1132
- ISSN
- 1043-1802 (ISSN-L)
- 1520-4812
- OpenAlex
- W2093390138
- Cited by
- 350
- References
- 0
- FWCI
- 3.86
- Type
- journal article
- Language
- en
- Open access
- closed
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- Bellocq, N. C., Pun, S. H., Jensen, G. S., & Davis, M. E. (2003). Transferrin-Containing, Cyclodextrin Polymer-Based Particles for Tumor-Targeted Gene Delivery. Bioconjugate Chemistry. https://doi.org/10.1021/bc034125f
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