Intraoperative Detection and Eradication of Residual Microtumors with Gap-Enhanced Raman Tags

The inability to intraoperatively diagnose and eliminate microscopic residual tumors represents a significant challenge in cancer surgery. These residual microtumors cause lethal recurrence and metastasis. Herein, we show a crucial example of Raman imaging with gap-enhanced Raman tags (GERTs) to serve as a robust platform for intraoperative detection and eradication of residual microscopic foci, which exist in surgical margins, tumor invasion, and multifocal tumor spread. The GERTs feature gap-enhanced gold core-shell nanostructures, with Raman reporters embedding inside the interior gap junction. This nanostructure elicits highly sensitive and photostable Raman signals for microtumor detection by applying a 785 nm, low-energy laser and produces hyperthermia effects for microtumor ablation upon switching a 808 nm, high-power laser. In the orthotopic prostate metastasis tumor model, systematic delivery of GERTs enabled precise imaging and real-time ablation of macroscopic malignant lesions around the surgical bed without damaging normal tissues. Consequently, the GERTs-based surgery prevented local recurrence and delivered 100% tumor-free survival. These results suggest the efficiency of theranostic GERTs for precise detection and removal of residual miroctumors, broadening the avenues to apply Raman-based imaging for theranostic precision medicine.