Simultaneous Response of Mitochondrial MicroRNAs to Identify Cell Apoptosis with Multiple Responsive Intelligent DNA Biocomputing Nanodevices

Challenges remained in precisely real-time monitoringof apoptoticmolecular events at the subcellular level. Herein, we developed anew type of intelligent DNA biocomputing nanodevices (iDBNs) thatresponded to mitochondrial microRNA-21 (miR-21) and microRNA-10b (miR-10b)simultaneously which were produced during cell apoptosis. By hybridizingtwo hairpins (H1 and H2) onto DNA nanospheres (DNSs) that had beenpreviously modified with mitochondria-targeted triphenylphosphine(TPP) motifs, iDBNs were assembled in which two localized catalytichairpins self-assembly (CHA) reactions occurred upon the co-stimulationof mitochondrial miR-21 and miR-10b to perform AND logic operations,outputting fluorescence resonance energy transfer (FRET) signals forsensitive intracellular imaging during cell apoptosis. Owing to thespatial confinement effects of DNSs, it was discovered that iDBNshad a high efficiency and speed of logic operations by high localconcentrations of H1 and H2, making the simultaneous real-time responsesof mitochondrial miR-21 and miR-10b reliable and sensitive duringcell apoptosis. These results demonstrated that iDBNs were simultaneouslyresponsive to multiple biomarkers, which greatly improved the detectionaccuracy to identify the cell apoptosis, demonstrating that iDBNsare highly effective and reliable for the diagnosis of major diseaseand screening of anticancer drugs.

Automated summary

Researchers developed a new type of intelligent DNA biocomputing nanodevices (iDBNs) for precise real-time monitoring of apoptotic molecular events. These nanodevices simultaneously responded to mitochondrial microRNA-21 and microRNA-10b produced during cell apoptosis, allowing sensitive intracellular imaging. This study demonstrated that iDBNs could effectively respond to multiple biomarkers, improving the detection accuracy for cell apoptosis and making them highly effective and reliable for disease diagnosis and anticancer drug screening.