A light and reduction dual sensitive supramolecular self-assembly gene delivery system based on poly(cyclodextrin) and disulfide-containing azobenzene-terminated branched polycations.

Novel reduction degradable and photosensitive disulfide-containing azobenzene-terminated branched poly(2-(dimethylamino)ethyl methacrylate)s (Az-ss-BPDMs) and supramolecular host-guest self-assembly systems with poly(cyclodextrin) (PCD) were prepared and evaluated as non-viral gene delivery vectors. The reduction and light dual sensitive properties of the supramolecular polycations PCD/Az-ss-BPDMs and their polyplexes PCD/Az-ss-BPDMs/DNA were confirmed by UV-Vis, SEC, DLS and zeta potential analyses, respectively. It was shown that the inclusion of PCD, introduction of disulfide bonds into branched polycations, increase of the branching degree of the branched Az-ss-BPDMs and use of UV irradiation could enhance the gene transfection efficiency and cellular internalization of the supramolecular disulfide-containing azobenzene-terminated branched polycationic polyplexes (PCD/Az-ss-BPDM/DNA). Importantly, the transfection efficiency of the light and reduction dual-sensitive supramolecular PCD/Az-ss-BPDM/DNA polyplexes achieved almost 10 times higher value than that of 25 kDa PEI control; whereas the cytotoxicity of the supramolecular polyplexes was lower than that of PEI control. Thus this light and reduction dual responsive supramolecular host-guest system containing azobenzene-terminated branched cationic polymers with disulfide bonds and PCD is a promising gene vector.