Iodine-mediated hydrogen-bonded organic framework and noble metal nanomaterial: A high-performance SERS platform for the detection of circulating tumor cells

Advances in nanostructured materials and liquid biopsy technologies are improving the detection and monitoring of carcinomas. As the application of biomedical surface-enhanced Raman spectroscopy (SERS) continues to evolve, the integration of porous organic frameworks (POFs) onto SERS platforms is yielding substantial signal enhancements, enabling the compositional analysis of rare circulating tumor cells (CTCs). The optimization of SERS bioprobes has shown accuracy in distinguishing cancerous cells from healthy ones. However, preparing such platforms with self-cleaning surfaces presents challenges at almost every stage, including limited chemical specificity, substrate reliability, instability, and the intricacies of detecting molecules in hot zones. These challenges often result in inconsistent performance due to inadequate molecular confinement and unfavorable orientation effects, triggered by suboptimal bonding chemistry. In this study, a self-cleaning Au@HOF/I 2 core-shell nanoparticle was successfully prepared. The SERS-active platform was developed via a solvothermal process, wherein a gold (Au) core is enveloped by a thin-layered hydrogen-bonded organic framework (HOF) in conjunction with an iodine-catalyzed reaction. Upon assessment, it achieved a detection limit of up to 5.12×10 –16 mol/L. During cancer diagnosis, at 25 min, the SERS-active bioprobe (Au@HOF/I 2 @4MBN@CS-HA@EpCAM) showcased remarkable sensitivity and specificity. With a 9.01×10 7 enhancement factor (EF) influenced by the local optical field and a limiting detection accuracy of 1 cell/mL, the bioprobe effectively targeted HeLa and MCF-7 cell lines as viable CTC models with capturing efficiencies of ≥94% and ≥98%, respectively. We anticipate that this contaminant-free SERS biosensor will furnish valuable diagnostic guidance and inspire new ideas for the precise identification of other disease-related biomarkers.