Long-Term Stable Eu₂O₃-Loaded Dendritic Mesoporous Silica Nanoprobes with Coordination-Enhanced Photoluminescence for Ultrasensitive Lateral Flow Immunoassay

Inorganic lanthanide nanomaterials as photoluminescent biolabels have attracted increasing attention due to their superior physicochemical properties. However, unstable conjugation of inorganic lanthanide nanomaterials with biological function units (such as antibodies) induces instability of conjugated complexes in aqueous solution, limiting their clinical application. In this study, we developed a rapid point-of-care testing (POCT) platform strategy based on coordination-enhanced time-resolved luminescence of specially nanostructural lanthanide particles for lateral flow immunoassay (CE-TRFIA). This strategy integrates a nanoprobe via a dendritic mesoporous silica nanosphere (DMSN) loading a large amount of ultrasmall amorphous europium oxide (Eu₂O₃) nanoparticles, which rapidly dissolve to release Eu³⁺ cations under neutral pH value and form luminescent complexes with photosensitizers (such as β-NTA and TOPO) in an LFIA system. This innovative strategy achieves high-sensitivity detection and long-term stability primarily through high-loading probes, excellent dissolution enhancement, stable covalent coupling, and time-resolved detection. With Procalcitonin (PCT) antigen selected as the detection sample, this approach achieves high-sensitivity detection of PCT with a limit of detection (LoD) as low as 1.9 pg/mL, significantly lower than that of commercial LFIA (0.1 ng/mL), and excellent clinical correlation (<i>r</i> = 0.989). The method offers chemiluminescence-level sensitivity without the need for large instruments while retaining the real-time detection characteristics of LFIA. Our results highlight CE-TRFIA as a highly sensitive, specific, and rapid POCT solution for detecting low-abundance biomarkers such as PCT, enhancing the diagnostic capabilities of traditional LFIA and offering significant potential for ultrasensitive and rapid clinical diagnostics.