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Published on: October 6, 2022
Construction of traceable cucurbit[7]uril-based virus-mimicking quaternary complexes with aggregation-induced
De-E Liu1, Xiangjie Yan, Jinxia An
1School of Material Science and Engineering, School of Chemistry and Chemical Engineering, Tianjin Key Laboratory of Drug Targeting and Bioimaging, Tianjin Enterprise Key Laboratory for Application Research of Hyaluronic Acid, Tianjin University of Technology, Tianjin 300384, P. R. China. ghhigher@hotmail.com hgao@tjut.edu.cn.
Abstract:
Construction of an efficient cationic gene delivery system with low cytotoxicity, high transfection efficacy, as well as gene tracking function remains a major challenge in gene therapy. Fabrication of simple and reversible nanocomplexes based on host-guest interaction provides an opportunity to construct stimuli-responsive intelligent supramolecular systems. Inspired by the hierarchical structure of viruses, a novel virus-mimicking PG/CB/TPE/DNA gene delivery system is developed via a multistep noncovalent self-assembly process between pDNA and the preformed PG/CB/TPE complexes based on the host-guest interaction between cucurbit[7]uril (CB[7]) and the protonated diamine group in the poly(glycidyl methacrylate)s derivative (PG), as well as the electrostatic interaction between para-carboxyl functionalized tetraphenylethylene (TPE) and cationic PG. The developed efficient multifunctional gene delivery system exhibits stimuli responsive characteristics and aggregation-induced emission phenomena, thereby enabling gene delivery pH responsiveness and traceability. Moreover, the introduction of TPE and CB[7] endows the self-assembled PG/CB/TPE/DNA complexes with virus-mimicking architecture and properties such as low cytotoxicity, high stability, excellent endosomal escape, and efficient transfection, which are expected to be used as a promising gene delivery system.
