Structural Effects of Carbohydrate-Containing Polycations on Gene Delivery. 3. Cyclodextrin Type and Functionalization
Abstract
Linear cationic β-cyclodextrin (β-CD)-based polymers can form polyplexes with plasmid DNA and transfect cultured cells. The effectiveness of the gene delivery and the cellular toxicity has been related to structural features in these polycations. Previous β-CD polycations were prepared from the cocondensation of 6^A,6^D-dideoxy-6^A,6^D-diamino-β-CD monomers with other difunctionalized monomers such as dimethyl suberimidate (DMS). Here, the type of CD and its functionalization are varied by synthesizing numerous 3^A,3^B-dideoxy-3^A,3^B-diamino-β- and γ-CD monomers. Both alkyl- and alkoxydiamines are prepared in order to vary the nature of the spacing between the CD and the primary amines in the monomers. These diamino-CD-monomers are polymerized with DMS to yield amidine-based polycations. The nature of the spacer between the CD-ring and the primary amines of each monomer is found to influence both molecular weight and polydispersity of the polycations. When these polycations are used to form polyplexes with plasmid DNA, longer alkyl regions between the CD and the charge centers in the polycation backbone increase transfection efficiency and toxicity in BHK-21 cells, while increasing hydrophilicity of the spacer (alkoxy versus alkyl) provides for lower toxicity. Further, γ-CD-based polycations are shown to be less toxic than otherwise identical β-CD-based polycations.
Additional Information
© 2003 American Chemical Society. Received 21 January 2003. Published online 22 March 2003. Published in print 1 May 2003. S.R.P. thanks the Department of Defense for an NDSEG fellowship. We would also like to thank Insert Therapeutics Inc. for partial support of this project. M.E.D. is a consultant to and has financial interest in Insert Therapeutics, Inc.Attached Files
Supplemental Material - bc034010b_s.pdf
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Additional details
- Eprint ID
- 73701
- DOI
- 10.1021/bc034010b
- Resolver ID
- CaltechAUTHORS:20170125-084654389
- National Defense Science and Engineering Graduate (NDSEG) Fellowship
- Insert Therapeutics Inc.
- Created
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2017-01-25Created from EPrint's datestamp field
- Updated
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2021-11-11Created from EPrint's last_modified field