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