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Cited by 350

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Transferrin-Containing, Cyclodextrin Polymer-Based Particles for Tumor-Targeted Gene Delivery

Bellocq, Nathalie C., Pun, Suzie H., Jensen, Gregory S., Davis, Mark E.·2003·Bioconjugate Chemistry

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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Authors
Bellocq, N. C., Pun, S. H., Jensen, G. S., & Davis, M. E.
Venue
Bioconjugate Chemistry
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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