A near-infrared-controlled and logic gate sensing platform for the sensitive and specific detection of dual miRNAs

Early detection of endometrial cancer remains challenging because of the lack of sensitive and specific diagnostic methods. This study develops a near-infrared (NIR)-activatable sensing platform with an AND logic gate to simultaneously detect miR-21 and miR-155, two promising endometrial cancer biomarkers. The sensing platform integrates acid-sensitive zeolitic imidazolate framework-8 (ZIF-8)-coated upconversion nanoparticles (UCNP@ZIF-8) with ternary DNA strands, consisting of a BHQ2-modified long strand (S2), a Cy5-labelled short strand (S3), and a photocleavable switch-bearing strand (S1). In a weakly acidic environment, the ZIF-8 shell decomposes to release UCNPs and DNA strands. Under 808 nm excitation, the UCNPs convert NIR light to ultraviolet or visible emission, cleaving the photocleavable linkers on S1 and exposing the toehold domain. The target miRNAs subsequently initiate a toehold-mediated strand displacement reaction, simultaneously displacing S1 and S3, thereby restoring Cy5 fluorescence. The biosensor demonstrated excellent sensitivity, with detection limits of 0.28 nM for miR-21 and 0.35 nM for miR-155. Validation in serum samples revealed recovery rates of 92-103.08%, confirming its potential for clinical application in complex biological environments.