Development of brain metastasis (BM) is most fequently seen in lung and breast cancers, associated with poor survival outcomes. Current imaging techniques can hardly delineate precise tumor margins to achieve complete surgical resection, which is the first line for a single BM. Here we aim to develop an intraoperative imaging approach to overcome the obstacle using targeted SERRS nanoprobes (NPs) towards the epidermal growth factor receptor (EGFR), whose signalling pathway is typically activated in BM. To attain superior sensitivity, we tuned a surfactant-free synthesis for SERRS NPs with surface plasmon resonance close to excitation in the near-infrared region and detected a concentration as low as 0.08 pM. Specific targeting was enabled by covalent coupling of EGFR antibodies, capable of differentiating a series of cancer cell lines with different expression levels. Such receptor-mediated targeting can be efficiently blocked by EGFR antibodies. Ex vivo imaging disclosed a primary distribution in the reticuloendothelial system. The high sensitivity, specificity, and stability of SERRS NPs provide a viable solution for intraoperative surgical guidance to resect remnant microscopic sattlitle metastases of BM, in addition to the primary tumor.

EGFR-targeted surface-enhanced resonance Raman scattering (SERRS) nanoprobes with subpicomolar sensitivity for detection of cancer brain metastases

ACS Spring 2022

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