Plasmon‐Enhanced NaYF ₄ :Yb/Er/Tm UCNPs Fluorescent Biosensing for Ultrasensitive Detection of GP73 in Clinical Liver Cancer Diagnosis

Early diagnosis of liver cancer demands high sensitivity, high specificity, convenience and real‐time monitoring capabilities. However, it encounters challenges such as low concentration of markers, numerous interfering factors, and limitations of detection technologies. This study investigates the potential of plasmonic gold nanorods (AuNRs) and rare‐earth‐based up‐conversion nanoparticles (NaYF 4 :Yb/Er/Tm UCNPs) in liver cancer surveillance and detection. A significant enhancement in Near‐infrared (NIR) fluorescence of the UCNPs was observed when the assay was used for detecting the serum biomarker Golgi protein 73 (GP73). The method enables ultra‐sensitive, quantitative detection of GP73 at concentrations as low as 5 ng mL −1 in a short period of time, using only 10 μL of serum samples. It demonstrated a sensitivity of 88.90% and a specificity of 100%, surpassing conventional immunoassays and showing strong agreement with Magnetic resonance imaging (MRI) and computed tomography (CT) in prognostic performance. Compared to existing advanced detection methods, this approach exhibited superior performance in diagnostic accuracy, cost‐effectiveness, and time efficiency, highlighting its high practical value and transformative potential. Based on the findings of this study, the rare‐earth‐plasmonic hybrid nanomaterials in the GP73 detection method show promise for future liver cancer diagnostics. Despite its simplicity, it offers potential applications in community screening, intraoperative assessment, and postoperative monitoring.