Related Experiment Video
Updated: Aug 10, 2026
Reproducible 3D Glioblastoma Migration Assay with Magnetic Nanoparticle Mediated Spheroid Localization Under Hypoxic Conditions
Published on: May 12, 2026
Single-cell transcriptome-guided biomimetic magnetothermal hydrogel microspheres for multimodal eradication of
Nan Wu1,2, Xi Luan2, Bihe Yuan3
1Department of Neurosurgery, Huanhu Hospital Affiliated to Tianjin Medical University, Tianjin Medical University, Tianjin, 300070, PR China.
Abstract:
Incomplete resection and rapid postoperative recurrence remain major challenges in glioblastoma (GBM) treatment. Inspired by the self-healing microduct architecture of pine resin, we developed an injectable magnetothermal-responsive hierarchical hydrogel microsphere platform, HGM + Multi(+), for spatiotemporally programmed magnetothermal ablation, anti-angiogenic blockade, and targeted chemotherapy. The system integrates T7-modified, pH-responsive temozolomide nanocarriers in GelMA microspheres with bevacizumab and Fe3O4 nanoparticles in a HAMA matrix, enabling rapid magnetothermal heating and sequential dual-drug release. Cellular and release studies demonstrated receptor-mediated uptake and tumor-microenvironment-responsive drug release. In orthotopic GBM resection models, a single intracavitary administration under alternating magnetic field markedly suppressed recurrence, reducing tumor volume to approximately 5% of controls and doubling median survival. In the immunocompetent postoperative GL261/C57BL/6J model, longitudinal IVIS, H&E-based tumor area quantification, and Kaplan-Meier analysis further confirmed reduced recurrent tumor burden and prolonged survival. Single-cell transcriptomic profiling of 47,781 cells revealed extensive tumor microenvironment remodeling, including macrophage polarization toward M1-like states, alleviated T cell exhaustion, enhanced cytotoxic programs, and an approximately 37% reduction in cancer stemness. These findings were further supported by ex vivo tumor-sphere assays and reduced Sox9/Nestin expression in recurrent tumors. Intercellular communication analysis indicated strengthened antigen-presentation signaling and intensified interactions between T cells and myeloid cells. Together, the integrated therapeutic, histological, and single-cell transcriptomic data support HGM + Multi(+) as a versatile postoperative strategy for eliminating residual GBM and advancing intelligent biomaterials for oncology.
