UV light-triggered unpacking of DNA to enhance gene transfection of azobenzene-containing polycations

Abstract

This study demonstrates a strategy to enhance gene delivery via photoregulated gene unpacking from its vector. Photoresponsive polycationic vectors composed of a middle azobenzene moiety and two terminal blocks of poly[2-(dimethylamino)ethyl methacrylate], termed as Azo-PDMAEMA, are synthesized using a difunctional azobenzene-based initiator via atomic transfer radiator polymerization (ATRP). The Azo-PDMAEMA exhibits trans to cis isomerization under alternate Vis-UV irradiation, and is capable of condensing plasmid DNA into nanocomplexes. Hydrophobic azobenzene groups in the cationic polymers are shown to enhance the interaction of complexes with the cell membrane, thus improving cell uptake and transfection efficiency. Increased gene expression in COS-7 cells, HepG-2 cells and CHO-K1 cells is achieved after UV irradiation due to UV-triggered intracellular gene unpacking. Time-resolved fluorescence assays further indicate that the trans to cis photoisomerization of Azo-PDMAEMA induces less compacted complexes, contributing to more exposure of genes for transcription.