Homologous tumor cell exosome-based drug delivery system co-delivering temozolomide and resveratrol for orthotopic glioblastoma therapy

Temozolomide (TMZ) is the first-line chemotherapeutic agent for treating glioblastoma multiforme (GBM), but its potency is hampered by inevitable drug resistance and systematic toxicity. Novel strategies that can decrease drug-associated adverse events are urgently needed. Encouraged by the significant pro-apoptotic, anti-inflammatory, and anti-proliferative properties of resveratrol (RES), one of the most widely studied polyphenolic compounds in cancer therapy, we propose a synergistic therapeutic strategy by using the combination of TMZ and RES to inhibit GBM progression. Recently, exosomes (Exos) have received increasing attention as promising drug delivery alternatives with favorable intrinsic features. In this work, Exos derived from homologous U87 ​cells are developed to co-deliver TMZ/RES for GBM therapy, defined as U87-Exos@TMZ/RES. It is found that U87-Exos@TMZ/RES share various advantages, including intrinsic tumor-targeting accumulation with homologous effects, as well as enhanced antitumor activity with synergistic effects of TMZ and RES. Furthermore, the excellent therapeutic effect of U87-Exos@TMZ/RES is also achieved in orthotopic GBM models. Based on these results, this novel U87-Exos@TMZ/RES delivery platform can provide a promising systemic chemotherapy strategy for enhancing GBM treatment.