Annealing novel nucleobase-lipids with oligonucleotides or plasmid DNA based on H-bonding or π-π interaction: Assemblies and transfections. (September 2018)

• Record Type: Journal Article
• Authors: Ma, Yuan; Zhu, Yuejie; Wang, Chao; Pan, Delin; Liu, Shuang; Yang, Mengyi; Xiao, Zhangping; Yang, Xiantao; Zhao, Wenting; Zhou, Xinyang; Li, Yiding; Pan, Yufei; Sun, Jing; Wang, Shuhe; Guan, Zhu; Zhang, Lihe; Yang, Zhenjun
• Is Part Of: Biomaterials. Volume 178(2018)
• Page Start: 147
• Page End: 157
• Publication Date: 2018-09
• Subjects: Gene delivery -- Nucleobase-lipid -- Self-assembly -- Oligonucleotide -- Plasmid DNA; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2018.06.012
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: Lipid derivatives of nucleoside analogs have been highlighted for their potential for effective gene delivery. A novel class of nucleobase-lipids are rationally designed and readily synthesized, comprising thymine/cytosine, an ester/amide linker and an oleyl lipid. The diversity of four nucleobase-lipids termed DXBAs (DOTA, DNTA, DOCA and DNCA) is investigated. Besides, DNCA is demonstrated to be an effective neutral transfection material for nucleic acid delivery, which enbles to bind to oligonucleotides via H-bonding and π-π stacking with reduced toxicity in vitro and in vivo . Several kinds of nucleic acid drugs including aptamer, ssRNA, antisense oligonucleotide, and plasmid DNAs can be delivered by DXBAs, especially DNCA. In particular, G4-aptamer AS1411 encapsulated by DNCA exhibits cellular uptake enhancement, lysosome degradation reduction, cell apoptosis promotion, cell cycle phase alteration in vitro and duration prolongation in vivo, resulting in significant anti-proliferative activity. Our results demonstrate that DNCA is a promising transfection agent for G4-aptamers and exhibites bright application prospects in the permeation improvement of single-stranded oligonucleotides or plasmid DNAs. Graphical abstract: Outlined description: Novel nucleobase-lipids are synthesized, which can interact with nucleic acids via H-bonding or Pi-stacking after annealing strategy. One of them named DNCA exhibits more excellent delivery efficiency for plasmid DNAs and oligonucleotides, especial for G4-aptamer AS1411.