Histidine-enriched multifunctional peptide vectors with enhanced cellular uptake and endosomal escape for gene delivery. Issue 1 (30th November 2016)

• Record Type: Journal Article
• Authors: Meng, Zhao; Luan, Liang; Kang, Ziyao; Feng, Siliang; Meng, Qingbin; Liu, Keliang
• Is Part Of: Journal of materials chemistry. Volume 5:Issue 1(2017)
• Page Start: 74
• Page End: 84
• Publication Date: 2016-11-30
• Subjects: Materials -- Periodicals; Chemistry, Analytic -- Periodicals; Biomedical materials -- Research -- Periodicals; 543.0284
• DOI: 10.1039/c6tb02862d
• Languages: English
• ISSNs: 2050-750X

Abstract

Abstract : Peptide vectors offer a promising gene delivery approach because of their biocompatibility and ease of functionalization. Abstract : Peptide vectors offer a promising gene delivery approach because of their biocompatibility and ease of functionalization. This article describes the design and evaluation of a series of multifunctional peptides and their gene delivery abilities. The peptides were composed of a cell-penetrating segment, stearyl moiety, cationic amphiphilic α-helical segment, and cysteine and histidine residues. The proton sponge effect of histidine residues at low pH and the α-helical conformation should improve endosomal escape. Inclusion ofd -type amino acids should improve proteolytic stability. The conformation, particle size and zeta potential of peptide/DNA complexes were characterized by circular dichroism and dynamic light scattering. Gene transfection efficiency was investigated by fluorescence-activated cell sorting and confocal microscopy. Transfection efficiencies of the designed peptide vectors were better than those of C18 -C(LLKK)3 C-TAT and Lipo2000.d -Type peptide C18 -c(llhh)3 c-tat showed three times higher transfection efficiency at N/P ratios of 6 and 8 than Lipo2000 in NIH-3T3 and 293T cells. All peptides showed lower cytotoxicity than Lipo2000 in NIH-3T3 and 293T cells. In the presence of trypsin or serum in vitro, d -type peptides showed better stability thanl -type peptides. Overall, the designed histidine-enriched multifunctional peptide gene vectors promoted cellular uptake, endosomal escape and gene transfection.