Abstract
Raman spectroscopy offers unique molecular fingerprinting capability for cancer diagnosis and monitoring, yet its biomedical application is fundamentally limited by weak intrinsic signals and complex biological backgrounds. Composite Raman probes, particularly surface-enhanced Raman scattering (SERS)-based systems, overcome these limitations through synergistic electromagnetic and chemical enhancement combined with functional integration. By engineering plasmonic nanostructures, interfacial electronic states, and molecular architectures, composite Raman probes achieve synergistic electromagnetic and chemical enhancement while incorporating biorecognition units, reporter molecules, and protective coatings to improve stability, specificity, and biocompatibility. In recent years, these probes have evolved from simple signal tags into multifunctional platforms capable of ultrasensitive tumor biomarker detection, high-contrast imaging, surgical guidance, therapy monitoring, and dynamic analysis of the tumor microenvironment (TME). This review systematically summarizes recent advances in composite Raman probes for oncological applications, with an emphasis on material design strategies, enhancement mechanisms, and stimulus-responsive regulation. Representative applications at both molecular and tissue levels are highlighted, including nucleic acid, protein, and exosome detection, as well as in vivo imaging and microenvironmental sensing. Finally, current challenges and future perspectives toward clinical translation are discussed, aiming to provide guidance for the rational design of next-generation Raman probes for precision oncology.