Concurrent Modulation of Competitive Mechanisms to Design Stimuli-Responsive Ln-MOFs: A Light-Operated Dual-Mode Assay for Oxidative DNA Damage

The identification of biomolecules for disease diagnosis requires facile analytical technologies with high precision and reliability. Several signal transduction pathways have inspired the development of various bioanalytical systems. However, most systems are greatly limited by a single-mechanism/mode assay, which easily results in false-positive/negative results. Herein, a multiple-mechanism-driven optical biosensor for 8-oxo-2 '-deoxyguanosine (8-oxo-dG), an early pathological signature of DNA lesions and various diseases, is designed by assembling adenine as a recognition element, mellitic acid as energy donors and Eu3+ as signal reporters into one metal-organic framework (MOF) system. Significantly, by regulating the delicate competition between the different mechanisms, the fabricated single platform (Eu-ade-MOF) concurrently provides two switchable approaches for rapid qualitative (30 s and 4 min) and quantitive (ppb level) recognition of 8-oxo-dG in both complex artificial and real human urine environments. Compared with those single-mechanism/mode-driven detections, this light-operated dual-mode analysis system can inherently boost the analysis reliability and largely minimize the chances of false negatives/positives for a non-invasive diagnosis of DNA damage and related diseases. This work represents the first effort in designing a luminescent sensor coupling multiple mechanisms in a single interface to determine DNA damage degree and provides a new approach for developing multimode analysis platforms for human health monitoring.