Cell-penetrating peptide-labelled smart polymers for enhanced gene delivery

Abstract

Highly efficient gene delivery vehicles are pursued to progress gene therapy. In this study, we developed the cell‐penetrating peptide‐labelled and degradable gene carriers for efficient external gene transfection. The cationic carriers were prepared by coupling low‐molecular‐weight polyethylenimine (PEI800) with 4ʹ4‐dithiodibutyric acid (DA), and HIV‐1 Trans‐Activator of Transcription (TAT) was conjugated to the carriers as a penetrating peptide. The resulted PEI‐DA‐TAT was able to condense plasmid DNA (pDNA) into a complex with a hydrodynamic size of around 150 nm under a neutral condition. PEI‐DA‐TAT showed negligible cytotoxicity to both Hela and HEK 293 cells with the cell viability of more than 80% beyond the carrier concentration of 50 μg/mL. This new carrier displayed better performance in regard to DNA transfection efficiency in comparison with the carriers of non‐TAT labelled PEI‐DA, commercial PEI25K and low‐molecular‐weight PEI (PEI800). The transfection efficiency of PEI‐DA‐TAT was increased by 8% compared with PEI‐DA and PEI25K. The experimental findings suggested that the developed PEI‐DA‐TAT is a promising carrier for efficient DNA delivery with low cytotoxicity for gene therapy.