PGMA-based supramolecular hyperbranched polycations for gene delivery

Supramolecular chemistry has been widely applied in biomedical fields. It was reported that the topological structure has effects on the performance of gene delivery systems. Supramolecular polymer-like gene carriers with hyperbranched topological structures have still not been reported. In this work, a series of ethanolamine-functionalized polyglycidyl methacrylate (PGMA)-armed AB₂ type macromonomers were synthesized based on atom transfer radical polymerization. The AB₂ type macromonomers can self-assemble into supramolecular hyperbranched polymers by the host-guest interaction between adamantane and β-cyclodextrin. The biophysical properties of self-assembled and dissembled supramolecular hyperbranched polycations were evaluated in detail. The self-assembled supramolecular polycations with hyperbranched structures possessed higher pDNA condensation ability and much better gene transfection performances than the dissembled AB₂ type counterparts. The present work would provide a new venue for designing advanced high-performance supramolecular hyperbranched nucleic acid-delivery systems.