NDLI: Reducible, dibromomaleimide-linked polymers for gene delivery.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Tan, James-Kevin Y. Choi, Jennifer L. Wei, Hua Schellinger, Joan G. Pun, Suzie H.
Description	Country affiliation: United States Author Affiliation: Tan JK ( University of Washington, Department of Bioengineering and Molecular Engineering and Sciences Institute, William H. Foege Building, Box 355061, 3720 15th Ave NE, Seattle, WA 98195, USA. spun@uw.edu.)
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.
File Format	HTM / HTML
ISSN	20474830
Issue Number	1
Journal	Biomaterials Science
Volume Number	3
e-ISSN	20474849
Language	English
Publisher	Royal Society of Chemistry
Publisher Date	2015-01-01
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Subject Keyword	Discipline Biomedical Engineering Discipline Therapeutics
Content Type	Text
Resource Type	Article
Subject	Materials Science Biomedical Engineering

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