Construction of traceable cucurbit[7]uril-based virus-mimicking quaternary complexes with aggregation-induced emission for efficient gene transfection

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.