Embryonic Stem Cells-Derived Exosomes Endowed with Targeting Properties as Chemotherapeutics Delivery Vehicles for Glioblastoma Therapy

Exosomes are nanosized membrane vesicles (30-100 nm) that can easily penetrate the blood-brain barrier, safely deliver therapeutic drugs, and be modified with target ligands. Embryonic stem cells (ESCs) provide abundant exosome sources for clinical application due to their almost unlimited self-renewal. Previous studies show that exosomes secreted by ESCs (ESC-exos) have antitumor properties. However, it is not known whether ESC-exos inhibit glioblastoma (GBM) growth. In this study, the anti-GBM effect of ESC-exos is confirmed and then c(RGDyK)-modified and paclitaxel (PTX)-loaded ESC-exos, named cRGD-Exo-PTX are prepared. It is then investigated whether the engineered exosomes deliver more efficiently to GBM cells versus free drug alone and drug-loaded ESC-exos using an in vitro GBM model and in vivo subcutaneous and orthotopic xenografts model. The results show that cRGD-Exo-PTX significantly improves the curative effects of PTX in GBM via enhanced targeting. These data indicate that ESC-exos are potentially powerful therapeutic carriers for GBM and could have utility in many other diseases.