GSH-Activatable Aggregation-Induced Emission Cationic Lipid for Efficient Gene Delivery.
Yue-Rui YuanQiang LiuDeyu WangYu-Dan DengTing-Ting DuWen-Jing YiSheng-Tao YangPublished in: Molecules (Basel, Switzerland) (2023)
The key to gene therapy is the design of biocompatible and efficient delivery systems. In this work, a glutathione (GSH)-activated aggregation-induced-emission (AIE) cationic amphiphilic lipid, termed QM-SS-KK, was prepared for nonviral gene delivery. QM-SS-KK was composed of a hydrophilic biocompatible lysine tripeptide headgroup, a GSH-triggered disulfide linkage, and a hydrophobic AIE fluorophore QM-OH (QM: quinoline-malononitrile) tail. The peptide moiety could not only efficiently compact DNA but also well modulate the dispersion properties of QM-SS-KK, leading to the fluorescence-off state before GSH treatment. The cleavage of disulfide in QM-SS-KK by GSH generated AIE signals in situ with a tracking ability. The liposomes consisted of QM-SS-KK, and 1,2-dioleoylphosphatidylethanolamine (DOPE) (QM-SS-KK/DOPE) delivered plasmid DNAs (pDNAs) into cells with high efficiency. In particular, QM-SS-KK/DOPE had an enhanced transfection efficiency (TE) in the presence of 10% serum, which was two times higher than that of the commercial transfection agent PEI25K. These results highlighted the great potential of peptide and QM-based fluorescence AIE lipids for gene delivery applications.
Keyphrases
- fluorescent probe
- living cells
- high efficiency
- gene therapy
- single molecule
- ionic liquid
- dna methylation
- gene expression
- drug release
- oxidative stress
- genome wide
- molecular docking
- cell death
- crispr cas
- cell cycle arrest
- endoplasmic reticulum stress
- smoking cessation
- low cost
- liquid chromatography
- circulating tumor
- replacement therapy