Cancer Research Institute, Experimental Education/Administration Center, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, P. R. China.
Department of Radiotherapy, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, Guangdong, 511518, P. R. China.
Adv Mater. 2023 Nov;35(45):e2304187. doi: 10.1002/adma.202304187. Epub 2023 Oct 8.
Existing solid-nanoparticle-based drug delivery systems remain a great challenge for glioblastoma chemotherapy due to their poor capacities in crossing the blood-brain barrier/blood-brain tumor barrier (BBB/BBTB). Herein, fruit-derived extracellular-vesicle (EV)-engineered structural droplet drugs (ESDDs) are demonstrated by programming the self-assembly of fruit-derived EVs at the DOX@squalene-PBS interface, greatly enhancing the antitumor efficacy against glioblastoma. The ESDDs experience a flexible delivery via deformation-amplified macropinocytosis and membrane fusion, enabling them to highly efficiently cross the BBB/BBTB and deeply penetrate glioblastoma tissues. As expected, the ESDDs exhibit approximately 2.5-fold intracellular uptake, 2.2-fold transcytosis, and fivefold membrane fusion higher than cRGD-modified EVs (REs), allowing highly efficient accumulation, deep penetration, and cellular internalization into the glioblastoma tissues, and thereby significantly extending the survival time of glioblastoma mice.
现有的基于固态纳米颗粒的药物输送系统由于其穿越血脑屏障/血脑肿瘤屏障（BBB/BBTB）的能力较差，仍然是胶质母细胞瘤化疗的一大挑战。在此，通过在 DOX@squalene-PBS 界面上编程水果衍生细胞外囊泡（EV）的自组装，展示了由水果衍生 EV 工程化的结构液滴药物（ESDD），极大地提高了针对胶质母细胞瘤的抗肿瘤功效。ESDD 通过变形放大的巨胞饮作用和膜融合进行灵活的递药，使它们能够高效地穿越 BBB/BBTB 并深入穿透胶质母细胞瘤组织。正如预期的那样，ESDD 的细胞内摄取率提高了约 2.5 倍，转胞吞作用提高了 2.2 倍，膜融合提高了 5 倍，高于 cRGD 修饰的 EV（REs），从而能够高效地积累、深入穿透并将细胞内化进入胶质母细胞瘤组织，从而显著延长胶质母细胞瘤小鼠的存活时间。
