Ratiometric pH-responsive SERS strategy for glioma boundary determination

Abstract

Glioma is one of the most common intracranial malignant tumors worldwide. Since the glioma is invasive and lacks a clear boundary with normal brain tissue, the neurosurgeon can only determine the extent of surgical resection based on empirical experience. Thus, accurately demarcating its boundaries has become a major challenge for surgeons. Owing to the high glycolysis metabolism of glioma cells, the acidification of the extracellular fluid has become an indicator of glioma evolution. Herein, a ratiometric pH-responsive surface-enhanced Raman scattering (SERS) strategy was developed for the rapid identification of glioma boundaries. A sensing chip composed of silver nanoparticles self-assembled film was fabricated, followed by the self-assembly of a pH-responsive SERS reporter, 4-mercaptopyridine (4-MPY). The characteristic SERS peak ratios of 4-MPY change regularly under different pH conditions. The boundary of glioma invasion was determined by measuring the pH of waterdrops infiltrated by interstitial fluids. The technology enables accurate, non-invasive, and rapid determination of local pH, thereby maximizing the removal of tumor tissue while minimizing damage to normal tissue. This technique is more rapid and simple than intraoperative pathological detection and can be possibly used for intraoperative navigation.

Keywords: Extracellular fluid; Glioma boundary; Intraoperative navigation; SERS; pH sensing.