Synergistic Dual-Targeting Bacterial Extracellular Vesicles Delivering Paclitaxel for Precision Glioblastoma Therapy
Bo Sun, Zongqiang Lv, Rong Li, Yong Yan, Ning Luo, Hongxiang Wang, Chao Chen, Peiran Song, Jiacan Su, Han Liu, Juxiang Chen
Abstract
Glioblastoma (GBM) poses significant therapeutic challenges due to the restrictive blood-brain barrier (BBB) and blood-tumor barrier (BTB). To overcome these obstacles, we developed a dual-targeted nanodelivery system (AT-BEVs) based on engineered bacterial extracellular vesicles (BEVs). By integrating Angiopep-2 for LRP-1-mediated BBB transport and TAT peptide for enhanced tumor penetration, AT-BEVs achieve sequential barrier and tumor targeting. This platform effectively encapsulates hydrophobic chemotherapeutics such as paclitaxel (PTX) and enables tumor microenvironment-responsive drug release. In orthotopic GBM models, AT-BEVs loaded with PTX (AT-BEVs@PTX) showed improved brain tumor accumulation, inhibited tumor progression, and significantly extended survival. Our work presents a promising strategy to overcome dual delivery barriers in GBM and offers translational potential for targeted cancer therapy.