SERS‐Guided Precision Resection Combined with Photothermal‐Immunotherapy for Glioblastoma Recurrence Prevention

Abstract The poor prognosis of patients with glioblastoma (GBM) is primarily attributed to highly aggressive residual microtumors left after surgery, with nearly all patients experiencing recurrence within the narrow margins of the initially resected lesion. Effective GBM treatment necessitates both precise intraoperative guidance and effective postoperative adjuvant therapy. Here, a multifunctional nanoplatform is reported for SERS‐guided GBM resection (S), photothermal therapy (P), and immunotherapy (IT) in one, namely SPIT probes. The SPIT probe comprises an AuNS core, a Raman reporter layer, and genetically overexpressed SIRPα variants derived from macrophage membranes. It exhibits a robust and unique Raman signal, enabling precise intraoperative tumor resection. After surgical resection, its photothermal effect facilitates the ablation of residual microtumor foci. Furthermore, the overexpression of SIRPα variants on the macrophage membrane effectively blocks the CD47‐SIRPα pathway, enhancing macrophage‐mediated tumor cell phagocytosis. In combination with photothermal therapy, this approach amplifies the antitumor immune response. Experimental results demonstrate that this combination therapy achieves superior antitumor efficacy in an in situ GBM model, significantly suppressing tumor recurrence and extending the median survival time of mice by more than two fold. This all‐in‐one multifunctional nanotheranostic platform holds great promise for improving GBM treatment outcomes and effectively preventing tumor recurrence.