Customized Controllable Pyrophosphate Nanosensor Based on Lanthanide Metal–Organic Frameworks for Accurate and Sensitive Detection of Nucleic Acids
Long Yu, Yumin Feng, Qianqian Yuan, Shuang Peng, Yuxiu Xiao, Gaosong Wu, Xiang Zhou
Abstract
Pyrophosphate (PPi) and nucleic acid amplification play a critical role in medical diagnostics, making the development of precise nanosensors essential. Lanthanide metal–organic frameworks (Ln-MOFs) are increasingly recognized for their potential in advanced luminescent biosensing applications. However, research on customized controllable responses in Ln-MOF nanosensors is still lacking, which is critical for the molecular-level modular design. In this work, we introduce a ligand engineering strategy to regulate coordination-induced antenna effect emission in Ln-MOFs, optimizing their pyrophosphate (PPi) sensing from fluorescence turn-off to turn-on modes. By tuning the coordination environment through ligand programming, we discovered a “near coordination compensation” effect, allowing for controllable transitions between aggregation-induced emission and quenching (AIE/AIQ). This reversible response was supported by density functional theory calculations. Using a Eu 3+ /Tb 3+ dual-emission Ln-MOF designed with 2,6-pyridinedicarboxylic acid as the optimized ligand, we developed a self-correcting PPi nanosensor with a detection limit of 0.2 μM. Moreover, this system enabled ultrasensitive nucleic acid detection, achieving a limit of detection (LOD) as low as 1 fM, with applications in DNA pyrosequencing, qPCR, and DNA epigenetic modification (5-formylcytosine) analysis. These findings shed light on the structural and photophysical factors controlling Ln-MOF luminescence, offering a promising platform for highly accurate and sensitive nucleic acid detection in biomedical diagnostics.