Enhanced gene transfection efficiency by use of peptide vectors containing laminin receptor-targeting sequence YIGSR

This study presents the design and evaluation of a series of multifunctional peptides and their gene delivery abilities. The peptide sequences contained a cell-penetrating segment, six continuous histidine residues, a stearyl moiety and a laminin receptor-targeting segment. The YIGSR segment promoted cellular uptake through the interaction with laminin receptors on the surface of cells, which resulted in a great improvement in gene transfection efficiency. The conformation, particle size and zeta potential of peptide/DNA complexes were characterized via circular dichroism and dynamic light scattering. Their gene transfection efficiency was investigated by fluorescence-activated cell sorting and confocal microscopy. The transfection efficiency of the designed peptide vectors was higher than that of Lipo 2000. The peptide TAT-H₆-K(C₁₈)-YIGSR displayed transfection efficiencies at N/P ratios of 6, which was 3.5 and 7 times higher than that of Lipo 2000 in B16F10 and 293T cells, respectively. All peptides exhibited lower cytotoxicity than Lipo 2000 in B16F10 and 293T cells. In summary, the designed YIGSR-containing multifunctional peptide gene vectors promoted cellular uptake and gene transfection. Their in vivo transfection ability was investigated in zebrafish, and the transfection efficiency was determined by confocal microscopy and bioluminescence imaging. The peptide vectors, owing to their relatively short sequences and ease of functionalization, offer a promising approach for gene delivery because of their low cytotoxicity and high transfection efficiency.