ACS Appl Mater Interfaces. 2019 Jul 24;11(29):25654-25663. doi: 10.1021/acsami.9b01433. Epub 2019 Jul 9.
The reactive oxygen species (ROS)-responsive intelligent drug delivery system has developed rapidly in recent years. However, because of the low concentration of ROS in most types of tumor cells, it is not possible to rapidly and effectively stimulate the drug delivery system to release the active drug. Here, we introduced "sequential induced activation processes" for efficient tumor therapy by designing a new ROS-responsive drug release platform. β-Lapachone, a positively charged nitrogen mustard (NM) prodrug, and two diblock molecules (mPEG-AcMH and PAsp-AcMH) are self-assembled to form prodrug primary micelles, which are further aggregated into nanoparticles that facilitate drug codelivery. When administered by intravenous injection, the nanoparticles reach the tumor site and enter the tumor cells by endocytosis. The β-lapachone released in the tumor cells induces a large amount of HO, and the ROS-responsive NM prodrug is activated to form activated NM, quinone methide, and boric acid under the induction of HO. The activated NM leads to tumor cell apoptosis.
近年来，活性氧（ROS）响应型智能药物递送系统发展迅速。然而，由于大多数类型的肿瘤细胞中 ROS 浓度较低，因此无法快速有效地刺激药物递送系统释放活性药物。在这里，我们通过设计一种新的 ROS 响应型药物释放平台，引入了“顺序诱导激活过程”，以实现有效的肿瘤治疗。β-拉帕醌是一种带正电荷的氮芥（NM）前药，和两个两嵌段分子（mPEG-AcMH 和 PAsp-AcMH）自组装形成前药初级胶束，进一步聚集形成纳米颗粒，有利于药物共递。通过静脉注射给药，纳米颗粒到达肿瘤部位并通过内吞作用进入肿瘤细胞。β-拉帕醌在肿瘤细胞中释放，诱导大量 HO，ROS 响应型 NM 前药在 HO 的诱导下被激活，形成活化的 NM、醌甲醚和硼酸。活化的 NM 导致肿瘤细胞凋亡。
