Precise identification and detection of cancer cells using nanoparticle probes are critically important for early cancer diagnosis and subsequent therapy. We herein develop novel folate receptor (FR)-targeted surface-enhanced Raman scattering (SERS) nanoprobes for cancer cell imaging based on a click coupling strategy. A Raman-active derivative (5,5'-dithiobis(2-nitrobenzoic acid)-N (DNBA-N)) is designed with a disulfide bond for covalently anchoring to the surface of hollow gold nanoparticles (HAuNPs) and a terminal azide group for facilitating highly efficient conjugation with the bioligand. Modification of HAuNPs with DNBA-N yields monolayer coverage of Raman labels absorbed on the nanoparticle surface (HAuNP-DNBA-N) and strong SERS signals. HAuNP-DNBA-N can be simply and effectively conjugated with folate bicyclo[6.1.0]nonyne derivatives via a copper-free click reaction. The synthesized nanoprobes (HAuNP-DNBA-folic acid (FA)) exhibit excellent targeted capacities to FR-positive cancer cells relative to FR-negative cells through SERS mappings. The receptor-mediated delivery behaviors are confirmed by comparison with the uptake of HAuNP-DNBA-N and free FA competition experiments. In addition to its good stability and benign biocompatibility, the developed SERS nanoprobes have great potential for applications in targeted tumor imaging.
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