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[This article belongs to Volume - 70, Issue - 7]
Published on : 2025-07-21 14:54:37
Article Code: AMJ-21-07-2025-12323
Title : Engineered Exosomes Derived from Hypoxic Mesenchymal Stem Cells: Enhanced Blood-Brain Barrier Penetration for Glioblastoma Targeting
Author(s) : Dr. Ahmed Hassan, Dr. Lisa Park
Abstract :
Glioblastoma multiforme (GBM) treatment is hindered by the impermeable blood-brain barrier (BBB) and poor drug
bioavailability. This study characterizes exosomes isolated from mesenchymal stem cells (MSCs) cultured under 1%
O₂ hypoxic conditions and evaluates their BBB transcytosis capabilities. Hypoxic preconditioning significantly
enriched exosomal cargo with miR-126 and matrix metalloproteinase-9 (MMP-9), facilitating tight junction
modulation in human brain microvascular endothelial cells (hBMECs). Functionalized with chlorotoxin peptides,
these engineered exosomes demonstrated 8-fold higher accumulation in orthotopic GBM xenografts compared to
normoxic controls. Co-delivery of temozolomide and siRNA against MGMT achieved synergistic cytotoxicity in
patient-derived GBM spheroids. Our results establish hypoxic MSC-exosomes as a nature-inspired nanocarrier system
for brain tumor theranostics.