Journal
JOURNAL OF MATERIALS CHEMISTRY B
Volume 5, Issue 39, Pages 7963-7973Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c7tb01915g
Keywords
-
Categories
Funding
- National High Technology Research and Development Program (863 Program) of China [2014AA020707]
- National Natural Science Foundation of China [21176046/21503035/21606041]
- Fundamental Research Funds for the Central Universities [DC201502020205]
Ask authors/readers for more resources
Headgroups in cationic lipids play very important roles in determining transfection efficiency and toxicity in gene delivery. To better understand the influence of headgroups on gene delivery, a tri-peptidebased lipid was synthesized, wherein the usual quaternary ammonium was replaced by a tri-peptide. Though both the tri-peptide-based lipid (DAO3) and the quaternary ammonium-based lipid (DDCTMA) successfully mediated gene transfection, DAO3 was superior to DDCTMA in both in vitro and in vivo studies. Following their preparation into liposomes, the particle size, zeta potential, and DNA-binding capacity of the liposomes and lipoplexes were characterized to evaluate the efficiency of DAO3 compared to DDCTMA with regard to gene interactions. The expression of luciferase from pDNA mediated by DAO3 was 2-fold greater than than that with DDCTMA in Hep-2 cells, and DAO3/siRNA lipoplexes could silence about 60% luciferase in A549 cancer cells expressing firefly luciferase. DAO3/ Luc-siRNA treatment exhibited 3-fold the efficiency of DDCTMA/Luc-siRNA in terms of in vivo luciferase RNAi with the bare density ratio of 0.54 at 48 h. Furthermore, DAO3 could mediate IGF-1R siRNA to inhibit tumor growth through silencing the expression of the IGF-1R protein, whereas DDCTMA showed nearly no effects. Most importantly, DAO3 had no obvious toxicity in vitro and in vivo, due to the biocompatibility of the peptide headgroups. In conclusion, these results demonstrated that the replacement of the quaternary ammonium headgroup by tri-ornithine may increase transfection efficiency and decrease toxicity.
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