The analytical and biomedical potential of cytosine-rich oligonucleotides: A review

•An review on current trends in applications of cytosine-rich oligonucleotides.•Recent developed biosensors (e.g., to detect pH, glucose or silver ions) and drug-delivery biomaterials are introduced.•Examples of silver nanoclusters created on cytosine-rich DNA strands are given.•The future challenges in construction and applications of biotools based on C-rich strands are also pointed.

Polycytosine DNA strands are often found among natural sequences, including the ends of telomeres, centromeres, and introns or in the regulatory regions of genes. A characteristic feature of oligonucleotides that are rich in cytosine (C-rich) is their ability to associate under acidic conditions to form a tetraplex i-motif consisting of two parallel stranded cytosine-hemiprotonated cytosine (C·C+) base-paired duplexes that are mutually intercalated in an antiparallel orientation. Nanotechnology has been exploiting the advantages of i-motif pH-dependent formation to fabricate nanomachines, nanoswitches, electrodes and intelligent nanosurfaces or nanomaterials. Although a few reviews regarding the structure, properties and applications of i-motifs have been published, this review focuses on recently developed biosensors (e.g., to detect pH, glucose or silver ions) and drug-delivery biomaterials. Furthermore, we have included examples of sensors based on parallel C-rich triplexes and silver nanoclusters (AgNCs) fabricated on cytosine-rich DNA strands. The potential diagnostic and therapeutic applications of this type of material are discussed.

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