P07.11.A BIOMIMETIC NANOSYSTEM WITH HYBRID NEUTROPHIL-GLIOMA MEMBRANE TARGETS AND ELIMINATES MALIGNANT GLIOMAS

Abstract BACKGROUND Glioblastoma (GBM) is among the most aggressive adult brain tumors, with poor prognosis and high recurrence. Despite surgery and chemoradiotherapy, treatment remains ineffective due to the invasive nature of glioma cells and the lack of targeted postoperative options. Residual cancer cells often persist post-resection, underscoring the need for strategies that can specifically eliminate them. MATERIAL AND METHODS We developed a zeolitic imidazolate framework (ZIF-8) nanoparticle system, UFZ-HM, loaded with ursolic acid (UA) and Fe₃O₄, and coated with a neutrophil-glioma hybrid membrane. UA induces apoptosis, while Fe₃O₄ triggers ferroptosis via the Fenton reaction. The system leverages the dual targeting properties of neutrophil and glioma membranes. In vitro, we assessed cytotoxicity, ROS generation, mitochondrial disruption, and BBB penetration using CCK-8, live/dead staining, and a Transwell BBB model. In vivo, an orthotopic glioma model in mice was used to evaluate tumor targeting, therapeutic efficacy, and biosafety. RESULTS UFZ-HM showed strong glioma cell inhibition, effective BBB penetration, and significant induction of ferroptosis. In vivo, it markedly reduced tumor growth, prolonged survival, and exhibited high biosafety. CONCLUSION UFZ-HM demonstrates biosafety and dual-targeting capacity via inflammatory and homologous recognition. Its pH-responsive release enables precise drug delivery, effectively suppressing glioma growth and improving survival. UFZ-HM offers a promising nanoplatform for enhancing GBM therapy.