Biodegradable nanofibrous scaffolds enhance standard of care for glioblastoma via localized targeted therapy.

Combination therapy is a well-established clinical strategy for treating aggressive cancers, but its success has not translated to patients with glioblastoma multiforme (GBM)-the most aggressive malignancy of the central nervous system. In this study, we evaluated the effects of combining temozolomide (TMZ), the standard chemotherapeutic agent for GBM, with several candidate targeted therapies to improve current outcomes in a mouse model of GBM resection and recurrence. In vitro, the EGFR inhibitor, erlotinib (ERL), emerged as the most promising combination drug across a diverse panel of GBM cells. In vivo, the therapeutic response was enhanced through localized delivery. ERL was encapsulated into electrospun acetalated dextran (Ace-DEX) scaffolds (Ace-ERL), a biodegradable and biocompatible polymer system that enables tunable degradation and controlled drug release. Local delivery of Ace-ERL to the resection cavity improved the pharmacokinetic profile and, when combined with systemic TMZ, significantly enhanced survival in a patient-derived xenograft mouse model. These findings support a novel translational approach to leverage combination therapy in GBM by pairing targeted delivery with standard chemotherapy.