High-affinity poly-cytosine DNA modulated metal-organic framework-DNA interactions and their application in detection of hepatocellular carcinoma biomarker.

Recent advances in DNA-metal-organic framework (MOF)-based label-free biosensors have demonstrated significant potential for the early diagnosis of hepatocellular carcinoma through synergistic integration of materials science and molecular biology. These platforms offer notable advantages in sensitivity and cost-effectiveness compared to conventional diagnostic methods. However, critical challenges persist, particularly in achieving stable DNA immobilization on MOF surfaces while simultaneously guaranteeing high hybridization efficiency-a dual requirement essential for reliable biosensing performance. To address this fundamental limitation, we systematically studied DNA-MOF interfacial interactions, using DNA homopolymers as model systems. Mechanistic key insights were gained from a comparative analysis of the adsorption/desorption dynamics of alpha-fetoprotein (AFP) aptamers and their homologous oligonucleotide competitors onto two iron-based MOFs (MIL-53(Fe) and MIL-88B(Fe)). The target-induced binding of the AFP-aptamer complex was insufficient to fully dissociate the probes from the MOF surfaces, thereby limiting signal transduction. Competitive displacement assays revealed that poly C DNA exhibited superior affinity, enabling efficient aptamer replacement via surface competition. Based on this mechanism, a label-free cascaded amplification DNA biosensor was constructed, where poly C DNA-mediated aptamer release from MOF surface triggered rolling circle amplification (RCA) to generate repetitive DNA templates for in situ synthesis of silver nanoclusters (AgNCs) as fluorescence reporters. This DNA biosensor achieved sensitives AFP detection with a linear range of 10-100 ng mL and a detection limit of 2.3 ng mL. This work expounds the underlying mechanisms governing MOF-DNA interfacial behavior and establishes a critical roadmap for developing highly sensitive and operationally label-free MOF-DNA-based biosensors.