Summary: | Glioma is recognized as the most common and aggressive primary brain tumor in adults. Owing to the occurrence of drug resistance and the failure of drug to penetrate the blood-brain barrier (BBB), there is no effective strategy for the treatment of glioma. The main objective of this study was to develop a biomimetic glioma C6 cell membrane (C6M) derived nanovesicles (DOX-FN/C6M-NVs) loaded with doxorubicin (DOX) and ultra-small Fe nanoparticles (FN) for accomplishing the effective brain tumor-targeted delivery of DOX and improving anti-cancer efficacy via inducing collaborative apoptosis and ferroptosis. The findings revealed that employing C6M-NVs as a carrier significantly improved the therapeutic efficacy by enabling evasion of immune surveillance, facilitating targeted drug delivery to tumor sites, and minimizing cardiotoxicity and adverse effects associated with DOX. DOX-FN/C6M-NVs exhibited more potent anti-tumor effects as compared with free DOX by promoting DOX-mediated apoptosis and accelerating ferroptosis via the mediation of FN. This study suggested that DOX-FN/C6M-NVs as the potential inducer of ferroptosis and apoptosis conferred effective tumor suppression in the treatment of glioma.
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