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

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

  • Acta Biomater. 2025 Mar 16:S1742-7061(25)00192-8. doi: 10.1016/j.actbio.2025.03.019.
Wei Zhang 1,  Sisi Wang 2,  Yanlong Xing 1,  Xianzhu Luo 1,  Rui Wang 3,  Fabiao Yu 4
Affiliations

Affiliations

  • 1 Key Laboratory of Emergency and Trauma, Ministry of Education, Key Laboratory of Hainan Trauma and Disaster Rescue, Key Laboratory of Haikou Trauma, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou 571199, PR China; Engineering Research Center for Hainan Bio-Smart Materials and Bio-Medical Devices, Key Laboratory of Hainan Functional Materials and Molecular Imaging, College of Emergency and Trauma, Hainan Medical University, Haikou 571199, PR China.
  • 2 Key Laboratory of Emergency and Trauma, Ministry of Education, Key Laboratory of Hainan Trauma and Disaster Rescue, Key Laboratory of Haikou Trauma, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou 571199, PR China; Engineering Research Center for Hainan Bio-Smart Materials and Bio-Medical Devices, Key Laboratory of Hainan Functional Materials and Molecular Imaging, College of Emergency and Trauma, Hainan Medical University, Haikou 571199, PR China; Department of Breast and Thyroid Surgery, The Second Affiliated Hospital, Hainan Medical University, Haikou 571199, PR China.
  • 3 Key Laboratory of Emergency and Trauma, Ministry of Education, Key Laboratory of Hainan Trauma and Disaster Rescue, Key Laboratory of Haikou Trauma, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou 571199, PR China; Engineering Research Center for Hainan Bio-Smart Materials and Bio-Medical Devices, Key Laboratory of Hainan Functional Materials and Molecular Imaging, College of Emergency and Trauma, Hainan Medical University, Haikou 571199, PR China. Electronic address: wangrui@muhn.edu.cn.
  • 4 Key Laboratory of Emergency and Trauma, Ministry of Education, Key Laboratory of Hainan Trauma and Disaster Rescue, Key Laboratory of Haikou Trauma, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou 571199, PR China; Engineering Research Center for Hainan Bio-Smart Materials and Bio-Medical Devices, Key Laboratory of Hainan Functional Materials and Molecular Imaging, College of Emergency and Trauma, Hainan Medical University, Haikou 571199, PR China. Electronic address: yufabiao@muhn.edu.cn.
PMID: 40101869 DOI: 10.1016/j.actbio.2025.03.019
Abstract

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.

Keywords

Bioluminescence imaging; Bioorthogonal label; Organ metastasis; Surface-enhanced raman scattering (SERS) imaging; Triple-negative breast cancer.

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