Exosomes Loaded with Gold Nanoparticles and Temozolomide for Targeted Therapy of Glioblastoma

Glioblastoma (GBM) is the highly aggressive and lethal primary tumor characterized by rapid growth, heterogeneity, and infiltration into surrounding brain tissues. Temozolomide (TMZ) is a key chemotherapeutic drug that is effective in GBM therapy. However, the effectiveness of TMZ is hindered by the blood–brain barrier (BBB). The BBB consists of multiple layers surrounded by blood vessels essential for protecting the central nervous system (CNS) and also limits the drug penetration within the brain. Exosomes are a class of extracellular vesicles secreted by various cells and have emerged as a promising drug delivery platform for treating GBM. Exosomes penetrate the BBB by multiple mechanisms, including receptor-mediated transcytosis, adsorptive mediated transcytosis, and endocytosis. Here, we developed a specific M1 macrophage-derived exosome (Exo)-based drug delivery nanoplatform against GBM. The TMZ and gold nanoparticles (AuNPs) were loaded into isolated Exo with the incubation method, and Exo-Au-TMZ was prepared. Here, we evaluated the anticancer effect of Exo-Au-TMZ on GBM in vitro and in vivo. The in vivo results showed that Exo-Au-TMZ has excellent BBB penetration and superior tumor accumulation and effectively inhibits tumor growth. In addition, Exo-Au-TMZ proved to be an excellent contrast agent for in vivo computed tomography (CT) imaging. We further validated the targeted accumulation of Exo-Au-TMZ by CT imaging. Overall, this study shows that Exo carrying TMZ and AuNPs can serve as a potentially powerful therapeutic nanoplatform for GBM treatment and could have utility in other central nervous system (CNS) disorders.