Add time:08/07/2019         Source:sciencedirect.com

A series of thiocholesterol-based cationic lipids (TCL) has been designed and synthesized by the attachment of thiocholesterol to a cationic amine via a disulfide bond. TCL can be incorporated into liposomes and used to package DNA into a lipoplex, thereby protecting it from DNase digestion. DNA is rapidly released from the complex in the presence of low concentrations of reducing agents. The lipoplex mediated efficient transfection activity and had low cytotoxicity. To improve the biocompatibility of the cationic lipoplex, TCL were used as a component in the assembly of a nanolipoparticle (NLP). The particle surface was subsequently modified by disulfide exchange to replace the cationic group with a negatively charged (glutathione) or zwitterionic (cysteine) reducing agent. A cell-binding ligand (TAT peptide, sequence GRKKRRQRRRGYG) was then incorporated onto the particle surface to enhance the particle–cell recognition. The sequentially assembled cell-binding NLP with a zwitterionic surface gave a larger transfection yield than the cationic NLP at all concentrations tested. At low DNA concentrations, the enhancement was 80-fold. The disulfide cationic lipids and the sequential assembly strategy enable one to tailor the surface charge, hydrophilicity, and recognition elements of a nanosized gene carrier. This results in increased gene transfer activity in a biocompatible particle.

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