Supramolecular host-guest polycationic gene delivery system based on poly(cyclodextrin) and azobenzene-terminated...

This article describes the supramolecular host-guest polycationic gene delivery system based on poly(β-cyclodextrin) (PCD) and azobenzene-terminated polycations. The azobenzene-terminated linear (Az-LPDM) and branched (Az-BPDM) cationic polymers were synthesized by atom transfer radical polymerization (ATRP) of 2-dimethylamino ethyl methacrylate (DMAEMA). The formation and photosensitive behavior of the supramolecular polycations of azobenzene-terminated polycations Az-LPDM and Az-BPDM with PCD were confirmed by UV-vis and NMR analysis. The supramolecular PCD/Az-BPDM/DNA and PCD/Az-LPDM/DNA polyplexes showed smaller size and were less positive than those of their corresponding polyplexes without PCD. Moreover, the UV irradiation may promote release of DNA from the photosensitive supramolecular polyplexes due to dissociation of supramoelcular polyplexes. In vitro experiments revealed that the photosensitive supramolecular polycationic polyplexes (PCD/Az-LPDM/DNA and PCD/Az-BPDM/DNA) exhibited enhancement of cellular uptake, higher transfection efficiency, and lower cytoxicity compared to the azobenzene-terminated polycation/DNA polyplexes in the absence of PCD. Branched polycationic polyplexes showed higher transfection efficiency than its linear polycationic polyplexes. Furthermore, after UV irradiation, the transfection efficiency of photosensitive supramolecular polyplexes was improved resulting from more DNAs delivered and released inside of the cell nuclei. Thus this photoresponsive supramolecular host-guest system containing azobenzene-terminated branched cationic polymers and PCD is a promising gene vector.