A controllable DNA: structural features and advanced applications of i-motif

Abstract

The i-motif consists of two parallel-stranded duplexes, stabilized by intercalated semi-protonated cytosine–cytosine (C·C⁺) pairing. Initially, the i-motif was thought to be unstable under physiological pH, which limited its biological interest. However, recent studies have demonstrated the presence of i-motifs in regulatory regions of the human genome at neutral pH, making their study biologically relevant. In addition, in the field of nanotechnology, the reversible pH-responsive properties of i-motif structures have been utilized to construct functional nanostructures for biomedical diagnostics and therapeutics. In this review, we present an overview of the structural features of i-motifs, the factors affecting their stability, and detection methods. Furthermore, we focus on summarizing recent advances in the application of i-motif-based functional nanostructures at the cellular level. The challenges and future prospects of i-motifs in nanomedicine are also discussed at the end of this paper.