A locoregional program of photothermal debulking, stemness suppression, and dendritic cell activation for durable...

Glioblastoma (GBM), especially in large or unresectable tumors, remains difficult to treat because of the lack of effective debulking, the persistence of therapy-resistant glioma stem cells (GSCs), and a profoundly immunosuppressive tumor microenvironment. Here, a locoregional hydrogel platform is developed to integrate photothermal debulking, post-ablation GSC suppression, and dendritic-cell-mediated immune activation for GBM therapy. The brain-compliant injectable hydrogel (MIN-PPIC@iGel) co-encapsulates indocyanine green/napabucasin-loaded micelles and poly(I:C)-loaded polymersomes, enabling staged local release for up to 20 days. After a single intratumoral administration followed by near-infrared irradiation, MIN-PPIC@iGel achieves surgery-mimetic photothermal cytoreduction, suppresses stem-like tumor phenotypes, and induces immunogenic cell death to generate tumor antigens and danger signals. Sustained release of poly(I:C) further activates dendritic cells and converts post-ablation tumor debris into in situ vaccines. In a large orthotopic GBM model, this single-shot locoregional therapy combined with anti-CTLA-4 renders 50% of mice tumor-free and establishes durable antitumor immunity. This work provides a material-programmed locoregional strategy for integrating local cytoreduction, stemness control, and immune activation against GBM.