| Summary: | Glioma is the most common malignant tumor of the nervous system in recent centuries, and the incidence rate of glioma is increasing year by year. Its invasive growth and malignant biological behaviors make it one of the most challenging malignant tumors. Maximizing the resection range (EOR) while minimizing the impact on normal brain tissue is crucial for patient prognosis. Changes in metabolites produced by tumor cells and their microenvironments might be important indicators. As a powerful spectroscopic technique, surface-enhanced Raman scattering (SERS) has many advantages, including ultra-high sensitivity, high specificity, and non-invasive features, which allow SERS technology to be widely applied in biomedicine, especially in the differential diagnosis of malignant tumor tissues. This review first introduced the clinical use of responsive SERS probes. Next, the sensing mechanisms of microenvironment-responsive SERS probes were summarized. Finally, the biomedical applications of these responsive SERS probes were listed in four sections, detecting tumor boundaries due to the changes of pH-responsive SERS probes, SERS probes to guide tumor resection, SERS for liquid biopsy to achieve early diagnosis of tumors, and the application of free-label SERS technology to detect fresh glioma specimens. Finally, the challenges and prospects of responsive SERS detections were summarized for clinical use.
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