Real-Time Intraoperative Surface-Enhanced Raman Spectroscopy-Guided Thermosurgical Eradication of Residual Microtumors in Orthotopic Breast Cancer

Residual microtumors following surgical resection are the major cause for lethal cancer recurrence. However, it remains challenging to completely eliminate these residual microtumors. Here, we report an integrated strategy for image-guided surgical resection of tumors and intraoperative surface-enhanced Raman spectroscopy (SERS) guided thermosurgical elimination of residual microtumors using a "three-in-one" theranostic nanoprobe, termed the Au nanostar-based photoacoustic (PA), SERS, and thermosurgical (starPART) probe. This starPART probe, comprising an Au nanostar core, a Raman molecule layer, and a silica outer layer, draws upon the significant advantages of PA imaging, SERS detection, and photothermal tumor ablation. These prominent features enable preoperative PA imaging for surgical resection of tumors and intraoperative SERS-guided thermosurgery for complete elimination of residual microtumors. In vivo experiments confirm complete eradication of microtumors without local recurrence and with a 100% tumor-free survivability. This work therefore offers a robust platform for real-time intraoperative eradication of residual microtumors with significant improvement of surgical outcomes.