肿瘤缺氧
提拉帕扎明
前药
血栓
医学
血栓形成
缺氧(环境)
血小板活化
癌症研究
材料科学
药理学
血小板
心脏病学
内科学
化学
放射治疗
生物化学
体外
氧气
细胞毒性
有机化学
作者
Heyou Han,Yifan Zhang,Xinxin Dai,Weiyun Zhang,Mohamed F. Foda,Jin Zhang,Yanli Zhao,Hao Han
标识
DOI:10.1002/adma.202104504
摘要
One of the main challenges for tumor vascular infarction in combating cancer lies in failing to produce sustained complete thrombosis. Inspired by the capability of vascular infarction in blocking the delivery of oxygen to aggravate tumor hypoxia, the performance of selective tumor thrombus inducing hypoxia activation therapy to improve the therapeutic index of coagulation-based tumor therapy is presented. By encapsulating coagulation-inducing protease thrombin and a hypoxia-activated prodrug (HAP) tirapazamine into metal-organic framework nanoparticles with a tumor-homing ligand, the obtained nanoplatform selectively activates platelet aggregation at the tumor to induce thrombosis and vascular obstruction therapy by the exposed thrombin. Meanwhile, the thrombus can cut off the blood oxygen supply and potentiate the hypoxia levels to enhance the HAP therapy. This strategy not only addresses the dissatisfaction of vascular therapy, but also conquers the dilemma of inadequate hypoxia in HAP treatment. Since clinical operations such as surgery can be used to induce coagulation, coagulation-based synergistic therapy is promising for translation into a clinical combination regimen.
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