Surface-engineered GE11-functionalized exosomes for EGFR-targeted peonidin delivery and suppression of SNAI1-mediated...

Glioblastoma is a highly aggressive and invasive brain tumor with poor prognosis, largely due to its rapid progression, epithelial-mesenchymal transition (EMT)-mediated invasiveness, and resistance to conventional therapies. Herein, the surface-engineered exosomal nanoplatform for targeted glioma therapy is functionalized glioblastoma-derived exosomes with the epidermal growth factor receptor (EGFR)-targeting GE11 peptide and loading them with peonidin (PN), a naturally occurring anthocyanin with anticancer potential. The engineered Exo-GE11/PN nanoparticles exhibited favorable physicochemical characteristics, including nanoscale size distribution, high encapsulation efficiency, colloidal stability, and preserved exosome morphology. GE11 functionalization significantly enhanced cellular uptake in EGFR-overexpressing glioma cells, facilitating efficient intracellular delivery of PN. In vitro studies demonstrated that Exo-GE11/PN effectively suppressed glioma cell proliferation, migration, and invasion while promoting apoptotic cell death. Mechanistic investigations revealed that the formulation attenuated EMT through downregulation of SNAI1 and modulation of the PI3K/Akt/NF-κB signaling pathway, accompanied by restoration of epithelial markers and suppression of mesenchymal markers. Furthermore, Exo-GE11/PN significantly reduced tumor growth and improved survival in glioma-bearing mice without inducing clear systemic toxicity, confirming its biocompatibility and therapeutic efficacy. Collectively, these findings highlight the importance of exosome surface engineering for targeted drug delivery and demonstrate that GE11-functionalized exosomes serve as an effective biointerface-mediated carrier for peonidin. This biomacromolecular nanoplatform offers a promising strategy for EGFR-targeted glioblastoma therapy through the suppression of EMT-associated oncogenic signaling pathways.