Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China; Hunan Provincial Engineering Research Centre of Translational Medicine and Innovative Drug, Changsha, China; Institute of Clinical Pharmacy, Central South University, Changsha, China.
Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China; Institute of Clinical Pharmacy, Central South University, Changsha, China.
J Control Release. 2021 Aug 10;336:510-521. doi: 10.1016/j.jconrel.2021.07.004. Epub 2021 Jul 6.
Exosomes (Exos) are promising vehicles for brain drug delivery due to nanosize and the ability to breach the blood-brain barrier (BBB). But the low yield of natural exosomes limits its application for nanomedicine. The generation of bioinspired nanovesicles (BNVs) that mimicking Exos is attractive, but there is a lack of comparative evaluation of Exos and BNVs. Here, we perform the first head-to-head comparison study of Exos and BNVs for brain tumor drug delivery. We show that BNVs derived from brain-derived endothelial cells are competent alternative nanocarrier to natural exosomes. The drug-loading capacity of Exos and BNVs are similar, but the yield of BNVs is substantially higher (500-fold) than Exos. Doxorubicin (DOX)-loaded BNVs (BNV/DOX) and DOX-loaded Exos (Exo/DOX) showed similar pharmacokinetic profiles and prolonged circulation od DOX. Despite inconsistent mechanisms, BNV/DOX can across the BBB, and exhibit suppression effects similar to Exo/DOX on the progress of glioblastoma (GBM) in zebrafish and in vivo subcutaneous and orthotopic xenografts mice models, with minimal systemic toxicity. Findings from this head-to-head comparison study indicate that autologous BNVs is a effective alternative of Exos for brain tumor nanomedicine.
外泌体（Exos）由于纳米尺寸和穿透血脑屏障（BBB）的能力，是用于脑部药物递送的有前途的载体。但是天然外泌体的产量低限制了其在纳米医学中的应用。仿生纳米囊泡（BNVs）的产生模仿了 Exos，这很有吸引力，但缺乏对 Exos 和 BNVs 的比较评估。在这里，我们首次对头对头比较研究 Exos 和 BNVs 用于脑肿瘤药物递送。我们表明，源自脑内皮细胞的 BNVs 是天然外泌体的有能力的替代纳米载体。Exos 和 BNVs 的载药能力相似，但 BNVs 的产量要高得多（500 倍）。阿霉素（DOX）负载的 BNVs（BNV/DOX）和 DOX 负载的 Exos（Exo/DOX）显示出相似的药代动力学特征，并延长了 DOX 的循环时间。尽管机制不一致，但 BNV/DOX 可以穿透 BBB，并在斑马鱼和体内皮下和原位异种移植小鼠模型中对神经胶质瘤（GBM）的进展表现出与 Exo/DOX 相似的抑制作用，而全身毒性最小。这项头对头比较研究的结果表明，自体 BNVs 是脑肿瘤纳米医学中 Exos 的有效替代品。
