College of Health Science and Engineering, Hubei University, Wuhan 430062, P. R. China.
College of Chemistry and Chemical Engineering, Hubei University, Wuhan 430062, P. R. China.
ACS Appl Mater Interfaces. 2023 Jul 5;15(26):31150-31158. doi: 10.1021/acsami.3c03001. Epub 2023 Jun 20.
Fabrication of ingenious nanomedicines to penetrate the blood-brain barrier (BBB) and blood-brain-tumor barrier (BBTB) for efficient glioblastoma (GBM) therapy remains a big challenge. In this work, macrophage-cancer hybrid membrane-camouflaged nanoplatforms were fabricated for target gene silencing-enhanced sonodynamic therapy (SDT) of GBM. The J774.A.1 macrophage cell membrane and the U87 glioblastoma cell membrane were fused to create a hybrid biomembrane (JUM) with good BBB penetration and glioblastoma targeting capability for camouflaging. The ZIF-8 nanoparticles were synthesized for indocyanine green (ICG) and HIF-1α siRNA encapsulation (ICG-siRNA@ZIF-8, ISZ) with a high loading efficiency. After accumulation in the tumor sites, the pH sensitivity of the nanoplatform enabled release of ICG and HIF-1α siRNA in the tumor cells. Then, the expression of HIF-1α could be efficiently inhibited by the released HIF-1α siRNA to increase the SDT efficiency under hypoxic conditions. and experiments revealed that ISZ@JUM showed good BBB penetration and brain tumor-targeting capability and could achieve effective gene silencing-enhanced SDT, demonstrating great promise for clinical applications.
为了实现高效的脑胶质瘤（GBM）治疗，研制能够穿透血脑屏障（BBB）和血脑肿瘤屏障（BBTB）的巧妙纳米药物仍然是一个巨大的挑战。在这项工作中，制备了巨噬细胞-癌细胞杂合膜伪装的纳米平台，用于增强靶向基因沉默的声动力学疗法（SDT）的 GBM。J774.A.1 巨噬细胞膜和 U87 脑胶质瘤细胞膜融合，产生具有良好 BBB 穿透性和脑胶质瘤靶向能力的杂合生物膜（JUM）用于伪装。合成了 ZIF-8 纳米粒子用于封装吲哚菁绿（ICG）和 HIF-1α siRNA（ICG-siRNA@ZIF-8，ISZ），具有高载药效率。在肿瘤部位积累后，纳米平台的 pH 敏感性使 ICG 和 HIF-1α siRNA 在肿瘤细胞中释放。然后，释放的 HIF-1α siRNA 可以有效地抑制 HIF-1α 的表达，在缺氧条件下提高 SDT 效率。体内和体外实验表明，ISZ@JUM 具有良好的 BBB 穿透性和脑肿瘤靶向性，可以实现有效的基因沉默增强的 SDT，为临床应用提供了广阔的前景。
