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<p>MicroRNAs (miRNAs) are crucial in cancer progression, rendering them potential biomarkers for lung cancer diagnosis. Therefore, the advancement of precise and sensitive miRNA detection techniques is very important. This article presents an Exonuclease III (Exo-III) assisted triple cycles-based aggregation-induced emission (AIE) biosensor utilizing a split G-quadruplex for the label-free detection of lung cancer related miRNA. Initially, the DNAzyme-probe existed in an “OFF” state, with the two split G-quadruplex segments (G4-a and G4-b) tethered at the termini of probe p1 and separated due to the inflexible duplex structure created by partial complementarity between p1 and p2, leading to the quenching of malachite green (MG) fluorescence. Upon binding of the target miRNA, p2 was competitively removed from the DNAzyme-probe, facilitating the assembly of G4-a and G4-b into a full intermolecular G-quadruplex. This structural reconfiguration created intercalation sites for MG, thus generating a "ON" fluorescence signal. Moreover, Exo-III-facilitated target recycling augmented the detection signal by liberating supplementary target molecules, hence fostering the development of additional G-quadruplex structures and intensifying MG binding. This cascade reaction markedly enhanced detection sensitivity. The AIE biosensor demonstrated exceptional selectivity, identifying single-base mismatches, and attained a detection limit of 547 aM for miRNA-21. This G-quadruplex-based AIE biosensor, due to its noninvasive nature, simplicity, and high efficiency, possesses significant potential for clinical applications in the early diagnosis of lung cancer.</p>

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Exonuclease-III assisted triple cycles for sensitive and reliable detection of lung cancer-related microRNA using split G-quadruplex

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月2日

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  • Xuetao Li,
  • Wanyan Wu,
  • Tiantian Liu,
  • Tingting Hao

摘要

MicroRNAs (miRNAs) are crucial in cancer progression, rendering them potential biomarkers for lung cancer diagnosis. Therefore, the advancement of precise and sensitive miRNA detection techniques is very important. This article presents an Exonuclease III (Exo-III) assisted triple cycles-based aggregation-induced emission (AIE) biosensor utilizing a split G-quadruplex for the label-free detection of lung cancer related miRNA. Initially, the DNAzyme-probe existed in an “OFF” state, with the two split G-quadruplex segments (G4-a and G4-b) tethered at the termini of probe p1 and separated due to the inflexible duplex structure created by partial complementarity between p1 and p2, leading to the quenching of malachite green (MG) fluorescence. Upon binding of the target miRNA, p2 was competitively removed from the DNAzyme-probe, facilitating the assembly of G4-a and G4-b into a full intermolecular G-quadruplex. This structural reconfiguration created intercalation sites for MG, thus generating a "ON" fluorescence signal. Moreover, Exo-III-facilitated target recycling augmented the detection signal by liberating supplementary target molecules, hence fostering the development of additional G-quadruplex structures and intensifying MG binding. This cascade reaction markedly enhanced detection sensitivity. The AIE biosensor demonstrated exceptional selectivity, identifying single-base mismatches, and attained a detection limit of 547 aM for miRNA-21. This G-quadruplex-based AIE biosensor, due to its noninvasive nature, simplicity, and high efficiency, possesses significant potential for clinical applications in the early diagnosis of lung cancer.