Bioinspired Nanofibers Incorporating Radiocatalytic Nanoparticles to Capture Migratory Glioma Cells for Localized Radiosensitization and Inhibition of Tumor Recurrence.

Abstract

High-grade gliomas (HGGs) are typically associated with poor prognosis and short survival times due to their aggressive malignancy, despite maximal tumor resection as part of current standard treatment, posing significant clinical challenges. Recent studies have highlighted a key clinicopathological feature: white matter fiber tracts (WMs) can serve as migratory pathways for glioma cells, allowing them to adhere to and invade surrounding brain tissue, thereby contributing to recurrence. In this study, a bioinspired fiber membrane composed of aligned nanofibers was fabricated via electrospinning and designed for implantation into the post-resection cavity. These nanofibers mimic the topology of WMs, offering a biomimetic pathway for glioma cell adhesion and migration. In this way, infiltrating glioma cells are more likely to be trapped by the fiber membrane rather than continue to invade through natural WMs. To further boost the efficacy of radiotherapy, modified TiO2:C nanoparticles with enhanced radiocatalytic activity were synthesized and incorporated into the membrane. These nanoparticles function as radiosensitizers and are taken up by glioma cells, enhancing their susceptibility to radiation. Thus, following tumor resection, TiO2:C-incorporated nanofiber membrane can be placed in the surgical cavity to locally trap infiltrating glioma cells and induce apoptosis by increasing their radiosensitivity, thereby preventing tumor recurrence.