Virus-Inspired Self-Assembled Nanofibers with Aggregation-Induced Emission for Highly Efficient and Visible Gene Delivery

Abstract

High-efficiency gene transfer and suitably low cytotoxicity are the main goals of gene transfection systems based on nonviral vectors. In addition, it is desirable to track the gene transfer process in order to observe and explain the mechanism. Herein, inspired by viral structures that are optimized for gene delivery, we designed a small-molecule gene vector (TR4) with aggregation-induced emission properties by capping a peptide containing four arginine residues with tetraphenylethene (TPE) and a lipophilic tail. This novel vector can self-assemble with plasmid DNA to form nanofibers in solution with low cytotoxicity, high stability, and high transfection efficiency. pDNA@TR4 complexes were able to transfect a variety of different cell lines, including stem cells. The self-assembly process induces bright fluorescence from TPE, which makes the nanofibers visible by confocal laser scanning microscopy (CLSM). This allows us for the tracking of the gene delivery process.

Mild polyaddition and polyalkylation based on the carbon–carbon bond formation reaction of active methylene

“…These facts indicated that the ester groups were successfully reduced to hydroxyl groups, and the cyanogen groups were successfully reduced to amino groups. The reduction products with multiple OH and NH 2 groups may have a great application in gene delivery 28,29 and antibacterial materials. 30 Fig.…”

Biomimetic peptide self-assembly for functional materials

“…243 A similar system has been demonstrated using TR 4 , a small molecule with four Arg residues with an N-terminus functionalized with a tetraphenylethene and a lipophilic tail. The species self-assembles and hosts plasmid DNA 244 in virus-mimicking nanoparticles that have low cytotoxicity, high stability and high transfection efficiency. The self-assembly process further induces bright fluorescence from tetraphenylethene groups packing together, allowing tracking of gene delivery.…”

Design and applications of protein delivery systems in nanomedicine and tissue engineering

“…Fibers were also designed for gene delivery or gene silencing. For example, Zhang et al designed a gene vector made of a lipophilic tail, tetraphenylethene and a peptide containing four arginines named TR4 to self-assemble with pDNA, leading to the obtention of nanofibers [223]. As for Pinese et al, they chose the load siRNA in MSNs-PEI and to coat PCL fibers with these NPs [224].…”