Bioorthogonal SERS-bioluminescence dual-modal imaging for real-time tracking of triple-negative breast cancer metastasis.

Triple-negative breast cancer (TNBC) represents an aggressive subtype of breast cancer, characterized by early metastasis and a poor prognosis. Traditional imaging modalities often lack the sensitivity and molecular specificity required for the early detection of metastatic lesions. In this study, we developed a dual-modal imaging strategy that integrates surface-enhanced Raman scattering (SERS) and bioluminescence imaging probes, utilizing bioorthogonal labeling to track TNBC organ metastasis. The SERS probes were encapsulated with azide-labeled macrophage membranes to extend circulation time and enhance targeting efficiency. Additionally, bioorthogonal metabolic glycolengineering was employed to modify luciferase-labeled tumor cells (4T1-Luc) with bicyclo[6.1.0]nonyne (BCN) groups, facilitating precise binding between the probes and 4T1-Luc cells through click chemistry reactions. This dual-modal imaging approach enabled real-time monitoring of small metastatic lesions with high sensitivity, providing a non-invasive and accurate method for assessing tumor metastasis and therapeutic response in vivo. Our findings indicate that the dual-modal imaging technique, combining SERS and bioluminescence with bioorthogonal labeling, holds significant potential for advanced applications in oncology. STATEMENT OF SIGNIFICANCE: This study devised a surface-enhanced Raman scattering (SERS) and bioluminescence dual-modal imaging strategy integrated with a bioorthogonal label to address the challenge of tracking the metastasis of aggressive triple-negative breast cancer (TNBC). In contrast to conventional methods, this approach facilitated real-time, whole-body monitoring of tumor dissemination through bioluminescence. Simultaneously, it achieved the detection of micro-metastases in organs using SERS, thereby exceeding the sensitivity limitations of existing imaging techniques. Clinical validation with human samples further demonstrated its potential for non-invasive therapeutic assessment and early intervention. By bridging preclinical innovation and clinical requirements, this research offered a transformative tool for precision oncology. It is expected to attract the interest of researchers in the fields of biomedicine, nanotechnology, and cancer therapeutics.