A dual-excitation-driven full-component-responsive lanthanide-based metal-organic framework for switchable profiling of multi-disease markers

Accurate detection of multiple small end-metabolic biomarkers is more sensitive than large biomolecules to provide real-time feedbacks of physiological/pathological state, but is more challenging due to lack of specific identifying groups. Current optical platforms suffer from unsatisfactory resolutions to differentiate each target because they produce similar output to different targets using a single excitation, and inevitably involve non-functional components that increase chances of interacting with non-target molecules. Herein, by taking full advantage of each building unit’s functionality to integrate multivariate recognition elements in one interface, a dual-excitation-driven full-component-responsive metal-organic framework (MOF)-based luminescent probe, namely CeTMA-TMA-Eu, is successfully custom-tailored for detecting both pseudouridine (ψ) and N-acetylaspartate (NAA), the diagnostic hallmarks of cancer and neurodegenerative disorder. Remarkably, ψ interacts with MOF’s organic building unit (trimesic acid, TMA) and filters out its absorptions of 262 nm-light to reduce its energy transferred to Eu³⁺, while NAA induces the valence transition of Ce⁴⁺/Ce³⁺ nodes to improve the cooperative energy transfer efficacy from TMA and Ce³⁺ to Eu³⁺. As a result, this platform exhibits completely reverse photoresponses towards ψ (“switch-off” at 262 nm excitation) and NAA (“switch-on” upon 296 nm excitation), and demonstrates excellent selectivity and sensitivity in complex biofluids, with low detection limits of 0.16 and 0.15 µM, and wide linear ranges of 0–180 and 0–100 µM, respectively. Such full-component-responsive probe with dual-excitation-mediated reverse responses for multi-small targets intrinsically minimizes its interaction with non-target molecules and amplifies resolution to discriminate each target, providing a new strategy for improving assay accuracy of multi-small biomarkers in diagnostics.