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

Abstract

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.

Keywords

Glioblastoma multiforme / Exosomes / Combination therapy / Orthotopic models

CRediT authorship contribution statement

Xuemei Wang: Writing - original draft, Data curation. Tao Zhang: Data curation. Dandan Zhang: Writing - review & editing, Data curation. Yuxin Cao: Software, Investigation. Xinxin Wang: Validation, Investigation. Xiaowei Liu: Visualization, Data curation. Weili Yang: Software. Yingchao Liu: Conceptualization. Daquan Chen: Project administration, Methodology, Funding acquisition.

Ethics approval and consent to participate

All experimental procedures were performed in strict accordance with the ARRIVE guidelines. Sample processing and experimental operations complied with the operational and ethical guidelines of Provincial Hospital Affiliated to Shandong First Medical University, and were approved by the Animal Ethics Committee (Ethical Annotation License No.2023-083).

Data availability

The data generated or analyzed in this study have been included in article.

Funding

This funding was supported by the Taishan Scholar Foundation of Shandong Province (No.qnts20161035); Natural Science Foundation of Shandong Province (No. ZR2019ZD24, ZR2019YQ30); Graduate Innovation Foundation of Yantai University (GIFYTU). The Shandong Province Modern Agricultural Industrial Technology System Chinese Herbal Medicine System (SDAIT-20-06).

Conflict of interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgment

Thanks to Adobe Illustrator software for support of scientific schematic mapping.

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