Issue 1, 2015

Reducible, dibromomaleimide-linked polymers for gene delivery

Abstract

Polycations have been successfully used as gene transfer vehicles both in vitro and in vivo; however, their cytotoxicity has been associated with increasing molecular weight. Polymers that can be rapidly degraded after internalization are typically better tolerated by mammalian cells compared to their non-degradable counterparts. Here, we report the use of a dibromomaleimide-alkyne (DBM-alkyne) linking agent to reversibly bridge cationic polymer segments for gene delivery and to provide site-specific functionalization by azide–alkyne cycloaddition chemistry. A panel of reducible and non-reducible, statistical copolymers of (2-dimethylamino)ethyl methacrylate (DMAEMA) and oligo(ethylene glycol)methyl ether methacrylate (OEGMA) were synthesized and evaluated. When complexed with plasmid DNA, the reducible and non-reducible polymers had comparable DNA condensation properties, sizes, and transfection efficiencies. When comparing cytotoxicity, the DBM-linked, reducible polymers were significantly less toxic than the non-reducible polymers. To demonstrate polymer functionalization by click chemistry, the DBM-linked polymers were tagged with an azide-fluorophore and were used to monitor cellular uptake. Overall, this polymer system introduces the use of a reversible linker, DBM-alkyne, to the area of gene delivery and allows for facile, orthogonal, and site-specific functionalization of gene delivery vehicles.

Graphical abstract: Reducible, dibromomaleimide-linked polymers for gene delivery

Supplementary files

Article information

Article type
Paper
Submitted
10 Jul 2014
Accepted
01 Aug 2014
First published
12 Aug 2014

Biomater. Sci., 2015,3, 112-120

Reducible, dibromomaleimide-linked polymers for gene delivery

J. Y. Tan, J. L. Choi, H. Wei, J. G. Schellinger and S. H. Pun, Biomater. Sci., 2015, 3, 112 DOI: 10.1039/C4BM00240G

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