Journal
JOURNAL OF MATERIALS CHEMISTRY B
Volume 3, Issue 6, Pages 1068-1078Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c4tb01353k
Keywords
-
Categories
Funding
- National Natural Science Foundation of China [81202465, 51373080]
- National Key Technologies R & D Program for New Drugs of China [2012ZX09301003]
Ask authors/readers for more resources
To overcome barriers associated with gene delivery, a series of peptides consisting of multifunctional fragments, including a cationic amphiphilic alpha-helical antimicrobial peptide (AMP), a cell penetrating peptide (CPP), TAT, a stearyl moiety, and cysteine residues, were designed and synthesized for evaluation as non-viral gene vectors. TAT and AMP segments were utilized to mediate cellular uptake and endosomal escape, respectively. Stearyl moieties provide an intramolecular hydrophobic environment to promote AMPs to form an alpha-helical conformation in PBS, and this is beneficial for DNA binding, cellular uptake, and endosomal escape. The alpha-helical content of the peptides, as well as the particle size, zeta potential, and morphology of the peptide/DNA complexes, was characterized. Fluorescence activated cell sorting (FACS) and confocal microscopy data showed that the peptides were able to efficiently translocate a pGL3 control plasmid across the plasma membrane via endocytosis, and then they successfully evaded endosomal entrapment and possible metabolic degradation. Moreover, one of the peptide vectors exhibited a high transfection efficiency similar to that of Lipofectamine 2000, concomitant with lower cytotoxicity. Overall, a combination of the four functional segments tested was used to generate a non-viral gene vector that synergistically promoted cellular uptake, endosomal escape, and gene expression.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available