GSH-Activatable Aggregation-Induced Emission Cationic Lipid for Efficient Gene Delivery

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 biocompat...

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Published inMolecules (Basel, Switzerland) Vol. 28; no. 4; p. 1645
Main Authors Yuan, Yue-Rui, Liu, Qiang, Wang, Deyu, Deng, Yu-Dan, Du, Ting-Ting, Yi, Wen-Jing, Yang, Sheng-Tao
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 01.02.2023
MDPI
Subjects
aggregation-induced emission
Biocompatibility
cationic lipids
Cations - chemistry
Cytotoxicity
DNA - genetics
Enzymes
Fluorescence
gene delivery
Gene therapy
Gene Transfer Techniques
Genes
Genetic Therapy
Glutathione
Glutathione - genetics
Lipids
Lipids - chemistry
Liposomes - chemistry
Lysine
Peptides
quinoline-malononitrile
reduction responsive
Scientific imaging
Transfection
gene delivery
aggregation-induced emission
reduction responsive
quinoline-malononitrile
cationic lipids
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Summary: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.
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ISSN:1420-3049
1420-3049
DOI:10.3390/molecules28041645