Interaction kinetics of peptide lipids-mediated gene delivery
- PDF / 2,378,656 Bytes
- 14 Pages / 595.276 x 790.866 pts Page_size
- 83 Downloads / 196 Views
Journal of Nanobiotechnology Open Access
RESEARCH
Interaction kinetics of peptide lipids‑mediated gene delivery Yinan Zhao1, Tianyi Zhao2, Yanyan Du1, Yingnan Cao1, Yang Xuan1, Huiying Chen1, Defu Zhi1, Shutao Guo3*, Fangli Zhong4* and Shubiao Zhang1*
Abstract Background: During the course of gene transfection, the interaction kinetics between liposomes and DNA is speculated to play very important role for blood stability, cellular uptake, DNA release and finally transfection efficiency. Results: As cationic peptide liposomes exhibited great gene transfer activities both in vitro and in vivo, two peptide lipids, containing a tri-ornithine head (LOrn3) and a mono-ornithine head (LOrn1), were chosen to further clarify the process of liposome-mediated gene delivery in this study. The results show that the electrostatically-driven binding between DNA and liposomes reached nearly 100% at equilibrium, and high affinity of LOrn3 to DNA led to fast binding rate between them. The binding process between LOrn3 and DNA conformed to the kinetics equation: y = 1.663631 × exp (− 0.003427x) + 6.278163. Compared to liposome LOrn1, the liposome LOrn3/DNA lipoplex exhibited a faster and more uniform uptake in HeLa cells, as LOrn3 with a tri-ornithine peptide headgroup had a stronger interaction with the negatively charged cell membrane than LOrn1. The efficient endosomal escape of DNA from LOrn3 lipoplex was facilitated by the acidity in late endosomes, resulting in broken carbamate bonds, as well as the “proton sponge effect” of the lipid. Conclusions: The interaction kinetics is a key factor for DNA transfection efficiency. This work provided insights into peptide lipid-mediated DNA delivery that could guide the development of the next generation of delivery systems for gene therapeutics. Keywords: Peptide lipids, Interaction kinetics, Uptake, Gene release, Gene delivery Introduction Gene therapy is the technology to transfer exogenous normal gene into the target cells to correct or compensate disease caused by genetic defects and anomalies, so
*Correspondence: [email protected]; [email protected]; zsb@dlnu. edu.cn 1 Key Laboratory of Biotechnology and Bioresources Utilization of Ministry of Education, College of Life Sciences, Dalian Minzu University, Dalian 116600, China 3 Key Laboratory of Functional Polymer Materials of Ministry of Education, State Key Laboratory of Medicinal Chemical Biology and Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China 4 School of Chemistry and Pharmaceutical Engineering, Jilin Institute of Chemical Technology, Jilin 132022, China Full list of author information is available at the end of the article
as to achieve the aim of treating disease [1, 2]. Peptidebased cationic lipids are promising nonviral tools for nucleic acid delivery into cells, e.g., plasmids DNA for transfection and siRNA for gene silencing [3–6]. They have shown to possess properties that are superior to those of other cationic lipids, such as good biodegradability, excellent
Data Loading...
