Plasmonic surgery: SERS-active smart nanotools reshaping intraoperative decision-making and precision therapy

Abstract

Traditional surgical procedures have long been constrained by the dual challenges of "visual limitations" and "temporal blind spots," relying on surgeons' visual and tactile assessments to determine tumor margins, with an average missed detection rate exceeding 25 %. Intraoperative frozen pathology, requiring 30–45 min, often leads to delayed decision-making. The emergence of surface-enhanced Raman scattering (SERS) technology has catalyzed the birth of "plasmonic surgery," a novel field offering revolutionary solutions to these limitations. This review systematically elucidates how SERS-active intelligent nanoplatforms, integrating molecular detection and precision therapeutic functions, are transforming intraoperative decision-making processes. Breakthrough technologies such as self-navigating SERS nanorobots and stimulus-responsive signal-amplifying probes are highlighted, alongside their applications in real-time tumor margin delineation and intraoperative molecular boundary alerts. Innovative integration of SERS with augmented reality navigation systems is discussed, demonstrating a closed-loop workflow from preoperative targeted enrichment to postoperative efficacy validation. Ethical challenges in SERS-guided intelligent surgery are also explored. Finally, future directions for next-generation SERS technologies are outlined. This review aims to provide interdisciplinary insights for surgeons, nanotechnologists, and medical device developers, advancing SERS from laboratory research to clinical practice and ultimately revolutionizing the paradigm of precision surgery.