Dopamine-Grafted Hyaluronic Acid Coated Hyperbranched Poly(β-Amino Esters)/DNA Nano-Complexes for Enhanced Gene Delivery and Biosafety

Gene therapy has attracted particular attention for the treatment of various genetic diseases, and the development of gene delivery vectors is of utmost importance for in vivo applications of gene drugs. Various cationic polymers with high nucleic acid loading and intracellular transfection efficiency have been reported, however, their biological applications are limited by potential toxicity. Surface modification is a robust solution to detoxify the cationic vectors, but this can inevitably weaken the transfection efficiency. To address this dilemma, we reported the ability of a dopamine (DA)-grafted hyaluronic acid (HA) to modify gene vectors for enhanced gene delivery and biosafety. The nano-vector was formed by using branched poly(beta-amino esters) (PAEs), and surface coating with HA-DA to form a core-shell nano-structure via electrostatic attraction. Upon HA-DA modification, the biosafety of the gene delivery vehicle was improved, as demonstrated by the cell cytotoxicity assay and hemolysis test. Notably, the nano-system displayed a DA-dependent transfection efficiency, in which a higher DA grafting degree resulted in better efficacy. This can be explained by the adhesive nature of DA, facilitating cell membrane interaction, as well as DA receptor mediated active targeting. At the optimal DA grafting ratio, the nano-system achieved a transfection efficiency even better than that of commonly used polyethylenimine (PEI) vectors. Together with its excellent biocompatibility, the vector presented here holds great promise for gene delivery applications.