Journal
BIOMACROMOLECULES
Volume 14, Issue 5, Pages 1587-1593Publisher
AMER CHEMICAL SOC
DOI: 10.1021/bm400221r
Keywords
-
Funding
- National Science Foundation [DMR 1005699]
- Division Of Materials Research
- Direct For Mathematical & Physical Scien [1005699] Funding Source: National Science Foundation
Ask authors/readers for more resources
Polycarboxybetaine esters (PCB-esters) can condense plasmid DNA into nanosized polyplexes for highly effective gene delivery with low toxicity. The design and characterization of tertiary CB-ester monomers and PCB-ester polymers are presented here to study the effects of molecular variation on functions important to nonviral gene transfer. Both buffering capacity and charge-shifting behavior can be tuned by modifying the distance between the charged groups and the ester size or type. A carbon spacer length (CSL) of one was found to bring the pK(a) of the tertiary amine into the optimal range for proton buffering. Ester hydrolytic degradation switches this polymer from cationic (DNA binding) to zwitterionic (DNA releasing) form while conferring nontoxicity. To allow rapid and externally controlled degradation, the effect of this charge-switching behavior on DNA release from polyplexes was directly studied with a novel photolabile PCB-nitrobenzyl ester (PCB-NBE). Photoinitiated ester degradation precipitated the rapid release of 72 +/- 5% of complexed DNA from PCB-NBE polyplexes. These insights reveal the key parameters important for the PCB-ester platform and the significance of charge switching to an effective and nontoxic nonviral gene delivery platform.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available