Drugless macro-to-nanogel conversion for reprogramming of malignant glioblastoma

Glioblastoma is the most fatal and aggressive brain tumour, posing significant clinical challenges due to its poor prognosis and high recurrence rate. Although surgical intervention remains the primary option for removing large tumour masses, their malignancy and recurrence often worsen after resection, emphasizing the urgent need for an effective postoperative strategy. Here, we present postoperative macro-to-nanogel therapeutics without loading anticancer chemical drugs, capable of effectively reprogramming malignant tumours into non-malignant cells while contributing to the preservation of brain function. The hydrogels with injectability and on-brain conformal filling are gradually dissociated to form nanogel therapeutics which are internalized in the residual tumour cells after resection surgery, significantly extending the survival of mice. Through spatially resolved transcriptomic analysis, the materials lead to multiple downregulations of cell cycle G1/S phase transition, the ERK1/2 cascade, the Wnt signalling pathway, and Ras protein signal transduction in the recurrent tumours.