School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, Dali University, Dali 671000, China.
J Control Release. 2024 Apr;368:170-183. doi: 10.1016/j.jconrel.2024.02.015. Epub 2024 Feb 23.
Due to the blood-brain barrier (BBB), the application of chemical drugs for glioblastoma treatment is severely limited. Recently, exosomes have been widely applied for drug delivery to the brain. However, the differences in brain targeting efficiency among exosomes derived from different cell sources, as well as the premature drug leakage during circulation, still limit the therapeutic efficacy. Here, we designed a functional oligopeptide-modified exosome loaded with doxorubicin (Pep2-Exos-DOX) for glioblastoma treatment. BV2 mouse microglial cell line was selected as the exosome source due to the favorable BBB penetration. To avoid drug release in the circulation, a redox-response oligopeptide was designed for incorporation into the membranes of exosomes to lock the drug during circulation. The enrichment of the drug in glioblastoma was confirmed. Pharmacodynamic evaluation showed Pep2-Exos-DOX possessed significant anti-cancer activity against glioblastoma as well as relative biosafety. This exosome-based drug delivery system modified with redox-response oligopeptides provides us a novel strategy for brain diseases treatment.
由于血脑屏障（BBB）的存在，化学药物在治疗脑胶质瘤方面的应用受到严重限制。最近，外泌体被广泛应用于脑部药物递送。然而，不同细胞来源的外泌体在脑靶向效率上的差异，以及在循环过程中过早的药物泄漏，仍然限制了其治疗效果。在这里，我们设计了一种功能性多肽修饰的载有多柔比星的外泌体（Pep2-Exos-DOX）用于治疗脑胶质瘤。由于具有良好的血脑屏障穿透性，我们选择 BV2 小鼠小胶质细胞系作为外泌体的来源。为了避免药物在循环中释放，我们设计了一种氧化还原响应性多肽并将其整合到外泌体的膜中，以在循环过程中锁定药物。药物在脑胶质瘤中的富集得到了证实。药效学评价表明，Pep2-Exos-DOX 对脑胶质瘤具有显著的抗癌活性和相对的生物安全性。这种用氧化还原响应性多肽修饰的基于外泌体的药物递送系统为脑部疾病的治疗提供了一种新的策略。
