POSS-cored and peptide functionalized ternary gene delivery systems with enhanced endosomal escape ability for efficient intracellular delivery of plasmid DNA

(TP-H12) was incorporated into their surface to obtain ternary gene delivery systems with enhanced endosomal escape ability. These ternary gene delivery systems exhibited low cytotoxicity towards ECs and possessed high REDV-mediated cellular uptake, excellent internalization efficiency, rapid endosomal escape and high nucleus translocation capacity. The endosomal escape of the ternary complexes was improved due to the pH buffering capacity of the histidine residue in TP-H12 and the optimized macropinocytosis internalization pathway. Moreover, these CPP-based ternary gene delivery systems have high gene delivery efficiency and could improve the migration of ECs as demonstrated by gene expression and transwell assay. These systems may serve as a promising candidate for gene delivery and transfection in ECs, which is advantageous for EC migration and endothelialization on the biomaterial surface.