AbstractIn this work, a biodegradable star-shaped copolymer poly(lactide-co-3(S)-methyl-morpholine-2,5-dione)6 (Star-(PLMD)6) was synthesized via ring-opening polymerization (ROP), and subsequently a gene carrier Star-PLMD-g-PEI-g-PEG-CREDVW was prepared by grafting polyethyleneimine (PEI), polyethylene glycol (PEG) and targeting peptide REDV onto Star-(PLMD)6. This gene carrier could form stable micelles to condense pEGFP-ZNF580 through electrostatic interaction. The resulting complexes were biocompatible and showed high efficiency in gene delivery. In addition, these complexes exhibited high selectivity for endothelial cells (ECs), high transfection efficiency and enhanced migration of ECs. The protein level of ZNF580 expression was significantly high (up to 85%), while the control group was only 51%. This combination of degradability, targeting ligand and star-structure strategy exhibits a significant advantage in transfection efficiency and migration of ECs.