A Fluorescence‐Free Electronic Resonance Raman Probe for Surgical Navigation and Postsurgical Photothermal Immunotherapy of Local Tumors and Distal Metastases
Abstract
Surgical resection of the primary tumor and simultaneous postsurgical adjuvant therapy for undetected metastases are the gold standard for the treatment of metastatic triple negative breast cancer (TNBC). Although near‐infrared fluorescent imaging/theranostic probes are widely used for TNBC, they suffer from photobleaching, low signal‐to‐background ratio, and insufficient photothermal conversion efficiency (PCE). To overcome these barriers, we developed a fluorescence‐free near‐infrared imaging probe that combines surface‐enhanced resonance Raman scattering (SERRS)‐guided surgery with photothermal immunotherapy. Two black hole quenchers (Q820/Q920) with near‐zero fluorescence background were designed and used to modify gold nanorods, yielding fluorescence‐free SERRS nanoparticles (NPs) with outstanding performance, including an ultralow detection limit (95 fM), ultrahigh signal‐to‐background ratio (69.9) in vitro and remarkable photostability, outperforming conventional fluorescent counterparts. Notably, these fluorescence‐free SERRS NPs exhibited a synergistic photothermal effect arising from quencher‐plasmon interactions, achieving a high PCE of 63.9%. Functionalized with a CXCR4 antagonist, the targeted SERRS NPs allow for intraoperative delineation of the tumor margin with an ultrahigh signal‐to‐background ratio of 22.6 for complete resection of the primary TNBC tumor. Combined with anti‐PD‐1 monoclonal antibody, the SERRS NPs effectively eliminated residual lesions and…
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