Precise co-delivery of drug and cytotoxic exosomes using a biomimetic nanorobot for glioma regression and recurrence prevention

Abstract

AbstractBackgroundAn increasing number of research studies have demonstrated the superiority of NK cells in clinical applications for cancer therapy. For a long time, the brain was considered as restricted area for immune cells because of the BBB, making the efficacy of NK cell-based immunotherapy on glioma is still insufficient. Therefore, a strategy to overcome the therapeutic bottlenecks of NK cell therapy for brain disease are urgently needed.In this study, we designed a biomimetic nanorobot termed “DTX@aNK Exos-NM” for enhancing the targeting ability and antitumor capacity. DTX@aNK Exos-NM was predesigned to have enhanced BBB penetration characterization and precise residual tumor targeting ability for delivery of both chemotherapeutic drugs and cytotoxic NK cell exosomes.ResultsThe biomimetic nanorobot was successfully established with both NK cell-liked and neutrophil-liked properties, as well as high loading efficiency and encapsulation efficiency of cytotoxic exosomes and chemotherapy drug. The transwell BBB model and C6-Luc glioma model in vivo study showed that DTX@aNK Exos-NM could penetrate the BBB and migrate to the residual tumor area efficiently in response to the inflammatory factors and Hsp70. In addition, DTX@aNK Exos-NM could effectively inhibit tumor proliferation and prolong survival time in a glioma mouse model.ConclusionOur results indicate that the the well-designed DTX@aNK Exos-NM not only enhances the antitumor effect of NK cells but also efficiently promoting cellular uptake of cytotoxic exosomes and DTX by endothelial cells and tumor cells. The co-delivery of chemotherapeutic drugs and cytotoxic exosomes could slow the recurrence of residual tumor growth and significantly improves survival. This personalized both drugs and exosomes delivery platform responsive to post-radiotherapy microenvironment may provide a new opportunity for cancer treatment.