Here, we utilized inert Cu@poly(styrene-alt-maleic acid) (PSMA) nanoparticles (NPs) as a potential starting material, enabling restrictions on chemical etching and resistance to external toxic surfactant adsorption. Such modulated oxidation−dissolution of Cu allowed preservation of the original nano-Cu shape and facilitated the subsequent deposition of Au atoms to form AuCu nanoshells with a tunable Au/Cu ratio. An increase in the Au concentration fraction at the surface nanolayer of the Au x Cu 1−x nanoshells (x = 0.41−0.86) could intensify the polarizability at the interface structure to essentially aid both electromagnetic fieldand chemical-improved surfaceenhanced Raman scattering (SERS). Among the Au x Cu 1−x composites, Au 0.86 Cu 0.14 nanoshells exhibited boost in SERS with amplification to 2−26fold that of pure Au nanorods, Ag@ polyvinylpyrrolidone (PVP) NPs, Ag@ PVP nanocubes, and Au y Ag 1−y @PSMA nanoshells. Because of the intended SERS response and lower cytotoxicity, we further conjugated the FGFR3 antibody onto the surface of the Au 0.86 Cu 0.14 nanoshells to first demonstrate SERS detection for the highly selective sensing and recognition of T24 human bladder cells. Time-dependent SERS monitor presented the targeted labeling with a signal increase from 0 to 24 h followed by an endocytosis route. In bladder cancer cell uptake, the Au 0.86 Cu 0.14 nanoshell possessed very slight release of Cu species which could deliver a "secretion signal" to trigger the outward transportation of AuCu hollow NPs to leave bladder living cells, showing an alternative method with the potential Au−Cu composite to overcome previous inorganic SERS NPs that often encounter cellular accumulation and cannot be secreted.
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