Turn-on fluorescence sensing of histidine in body fluids: unveiling its oncogenic potential as a cancer risk biomarker

Histidine plays a crucial role in biological processes and is linked to cancer pathophysiology, making it a promising biomarker indicative of cancer risk. In this study, we developed a fluorescence turn-on probe using bovine serum albumin stabilized copper nanoclusters (CuNCs) quenched with Cu²⁺ for the selective detection of histidine. Cu²⁺ primarily quenches the fluorescence of CuNCs via the inner filter effect (IFE). Histidine restores fluorescence by chelating Cu²⁺, thereby reducing its quenching interaction with the nanoclusters and modulating the surface environment. Histidine also suppresses non-radiative decay via coordination, disrupting Cu²⁺ induced aggregation. The probe demonstrates sensitivity with a limit of detection (LOD) of 3.61 μM and specificity against various biomolecules. Real sample analyses of saliva using the probe confirmed excellent recovery rates, validating its potential for non-invasive cancer biomarker detection. Additionally, a preliminary paper strip assay confirmed the feasibility of point of care histidine sensing. This work shows the diagnostic and screening potential of CuNCs/Cu²⁺ probes for use at home and resource-limited settings.