Internally coupled concave nanobox@quantum dots nanoassemblies for SERS/fluorescence/colorimetric trimodal detection of prognostic biomarker in acute ischemic stroke

Herein, the concave nanobox@quantum dots (CNB@QD) nanoassemblies were developed for the SERS/fluorescence/colorimetric trimodal detection of the prognostic biomarker neuron-specific enolase (NSE) in acute ischemic stroke (AIS). The Au-core AuAg concave nanoboxes (Au@AuAgCNB) with internal gaps were fabricated by selective etching and deposition. The concave curvature, core size, edge length, wall thickness, and hollowness of Au@AuAgCNB were regulated to improve the surface-enhanced Raman scattering (SERS) performance of Au@AuAgCNB with an enhancement factor of 8.01 × 10⁷. The CdSe/ZnS quantum dots (QD) were electrostatically assembled to Au@AuAgCNB mediated by polyethylenimine (PEI) to acquire CNB@QD. CNB@QD simultaneously provides SERS, fluorescence, and colorimetric signals. Because of the electrostatic shielding and physical isolation of PEI, CNB@QD exhibited excellent non-interference between signals, optical stability, and biocompatibility. Moreover, the fluorescence and color intensity of the CNB@QD were optimized by tuning the PEI thickness and QD density. Notably, the color intensity of the CNB@QD could be observed with the naked eye or quantified with the smartphone App Color Picker for point-of-care testing (POCT). CNB@QD and magnetic beads (MB) were antibody-modified for trimodal detection of NSE. During testing, as the NSE concentration increased, MB bound more CNB@QD, and its SERS, fluorescence, and color intensity also increased. The trimodal detecting platform demonstrated outstanding ultra-sensitivity, specificity, accuracy, and convenience. Besides, clinical detection results indicated the prognostic predictive potential of the detection platform for AIS.