Self-Assembling Nanoparticles Orchestrate Cuproptosis-Immunotherapy Synergy to Suppress Postoperative Glioma Recurrence

Glioblastoma (GBM), the most aggressive primary malignant tumor of the central nervous system, poses significant therapeutic challenges. Standard treatments, including maximal surgical resection combined with temozolomide (TMZ) chemotherapy and radiotherapy, provide only temporary relief from tumor progression and are inadequate in preventing recurrence. Recurrent GBM often displays a more aggressive phenotype, marked by heightened malignancy and tumor stem cell traits, further complicating clinical management. To overcome these limitations, we have devised an albumin-based nanodelivery system (BSA@CTW-NPs) for the synergistic delivery of two therapeutic agents: wogonoside, a potent antitumor compound derived from traditional Chinese medicine, and TMZ, the frontline chemotherapeutic drug for GBM. This system uniquely incorporates Cu²⁺ as a modulator of the tumor microenvironment (TME) to amplify oxidative stress through a Fenton-like reaction. Additionally, we have employed a postoperative in situ implantation strategy utilizing hemostatic sponges, harnessing the power of chemodynamic therapy (CDT) and cuproptosis to exert antitumor effects. This approach also triggers immunogenic cell death (ICD), thereby activating a potent antitumor immune response. Our combined strategy significantly enhances tumor cell eradication and suppresses postoperative recurrence, presenting a promising translational framework for improving clinical outcomes in GBM.