Increased precision of orthotopic and metastatic breast cancer surgery guided by matrix metalloproteinase-activatable near-infrared fluorescence probes

Advanced medical imaging technology has allowed the use of fluorescence molecular imaging-guided breast cancer surgery (FMI-guided BCS) to specifically label tumour cells and to precisely distinguish tumour margins from normal tissues intra-operatively, a major challenge in the medical field. Here, we developed a surgical navigation system for real-time FMI-guided BCS. Tumours derived from highly metastatic 4T1-luc breast cancer cells, which exhibit high expression of matrix metalloproteinase (MMP) and human epidermal growth factor receptor 2 (HER2), were established in nude mice; these mice were injected with smart MMP-targeting and "always-on" HER2-targeting near-infrared (NIR) fluorescent probes. The fluorescence signal was imaged to assess in vivo binding of the probes to the tumour and metastatic sites. Then, orthotopic and metastatic breast tumours were precisely removed under the guidance of our system. The post-operative survival rate of mice was improved by 50% with the new method. Hematoxylin and eosin staining and immunohistochemical staining for MMP2 and CD11b further confirmed the precision of tumour dissection. Our method facilitated the accurate detection and complete removal of breast cancer tumours and provided a method for defining the molecular classification of breast cancer during surgery, thereby improving prognoses and survival rates.