Biomimetic nanoparticles facilitate homologous targeting and radiosensitivity in glioblastoma cells

Glioblastoma (GBM) treatment remains challenging due to therapeutic resistance and targeting difficulties. Radiotherapy efficacy is often limited. This study aimed to develop biomimetic iron oxide nanoparticles coated with GBM cell plasma membranes (NPPM) for targeted radiosensitization. We hypothesized NPPM could achieve homologous targeting and enhance radiation effects. NPPM (∼100 nm hydrodynamic diameter) were synthesized and characterized. In vitro, NPPM showed preferential uptake by target U87 MG GBM cells compared to controls, confirming targeting specificity, and exhibited minimal intrinsic toxicity. NPPM also demonstrated efficient traversal across an in vitro blood-brain barrier model. Crucially, pretreatment with NPPM significantly increased radiation-induced γ-H2AX foci (DNA double-strand breaks) in U87 MG cells. This enhanced DNA damage translated into significant radiosensitization, as demonstrated by reduced cell viability and markedly decreased clonogenic survival following irradiation (2–10 Gy) compared to irradiation alone. These findings indicate that NPPM effectively targets GBM cells and potentiates radiation efficacy in vitro, suggesting its potential as a targeted radiosensitizer for improving GBM radiotherapy.