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

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