Trimodal aptamer-regulated nanozyme biosensor with cross-validation for trace aldosterone detection toward integrated...

Depression is a complex psychiatric disorder characterized by persistent affective dysregulation and somatic symptoms. As a major global public health concern, its diagnosis still largely relies on subjective questionnaire-based assessments. Aldosterone (ALD), a mineralocorticoid hormone associated with chronic stress, has emerged as a promising objective biomarker for depression. However, its clinical application is impeded by both its exceedingly low concentration in physiological fluids and the shortcomings of conventional detection methods. Herein, we reported a multifunctional aptamer-regulated nanozyme biosensor that integrated colorimetric, fluorescent, and electrochemical modes for precise, sensitive, and trace-level ALD detection. The biosensor employed NH₂-Fe₃O₄ nanoparticles as a nanozyme scaffold, exploiting their oligonucleotide-tunable peroxidase-like catalytic activity, intrinsic fluorescence quenching capability, and excellent electrical conductivity. Upon ALD introduction, competitive desorption of 6-FAM-labeled aptamer from the nanozyme surface induced simultaneous signal changes across all three modalities. The biosensor exhibited a wide detection range (3 pg mL^-1 to 20 ng mL^-1) and an ultra-low limit of detection (LOD) of 1.016 pg mL^-1. It not only enabled accurate quantification of serum ALD levels in depressive rats across different treatment groups for drug efficacy evaluation, but also performed reliable analysis of ALD concentrations in clinical human serum samples for depression diagnosis. Notably, the biosensor also supported non-invasive detection of ALD in saliva and urine, demonstrating strong potential for point-of-care testing (POCT) owing to its simplicity and rapidity. This multimodal strategy offers a powerful and practical platform for the objective diagnosis and therapeutic monitoring of depression.