Wang Jingchen, Yang Jian, Liu Kang, Yuan Jiayu, Shi Yijie, Li Hongdan, Zhao Liang
School of Pharmacy, Jinzhou Medical University, Jinzhou, 121000, PR China.
Life Science Institution, Jinzhou Medical University, Jinzhou, 121000, PR China.
Mater Today Bio. 2023 Aug 29;22:100780. doi: 10.1016/j.mtbio.2023.100780. eCollection 2023 Oct.
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.
胶质瘤被认为是成人中最常见且侵袭性最强的原发性脑肿瘤。由于耐药性的出现以及药物无法穿透血脑屏障（BBB），目前尚无治疗胶质瘤的有效策略。本研究的主要目的是开发一种仿生胶质瘤C6细胞膜（C6M）衍生的纳米囊泡（DOX-FN/C6M-NVs），其负载有阿霉素（DOX）和超小铁纳米颗粒（FN），以实现DOX的有效脑肿瘤靶向递送，并通过诱导协同凋亡和铁死亡来提高抗癌疗效。研究结果表明，采用C6M-NVs作为载体可通过逃避免疫监视、促进药物靶向递送至肿瘤部位以及将与DOX相关的心脏毒性和不良反应降至最低，从而显著提高治疗效果。与游离DOX相比，DOX-FN/C6M-NVs通过促进DOX介导的凋亡并通过FN的介导加速铁死亡，表现出更强的抗肿瘤作用。本研究表明，DOX-FN/C6M-NVs作为铁死亡和凋亡的潜在诱导剂，在胶质瘤治疗中具有有效的肿瘤抑制作用。
