Development of Supramolecular Pseudo-Block Conjugates Based on Star-Shaped Polycation for DNA Delivery

Supramolecular assembly provides a new strategy for designing various gene carriers for deoxyribonucleic acid (DNA) delivery. In this work, supramolecular pseudo-block conjugates based on star-shaped polycation are developed as novel nonviral gene vector. First, cyclodextrin (CD) is selected as core and grafted with low molecular weight polyethylenimine (PEI 1800 ) as arms to obtain high molecular weight star-shaped polycation CD-PEI 8 (SCP). Then, azobenzene (Az) modified poly(ethylene glycol) is synthesized and named as azobenzene modified poly(ethylene glycol) (Az-PEG). Subsequently, the supramolecular pseudo-block conjugates are prepared via host–guest interaction between CD and Az. The result suggests that SCP/Az-PEG condenses DNA into spherical nanoparticles with sizes of around 150 nm. The in vitro experiment shows that the cell viability of DNA/SCP/Az-PEG polyplexes is significantly improved compared with that of PEI 25k /DNA polyplexes. The PEGylation does not decrease the cellular uptake efficiency and transfection efficiency. Furthermore, the cellular trafficking shows that PEGylation does not significantly influence nuclear entry. The star-shaped architecture of polycation plays an important role in gene delivery.