Department of Chemistry, Texas A&M University, College Station, TX, 77843-3255, USA.
Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
Angew Chem Int Ed Engl. 2018 May 14;57(20):5725-5730. doi: 10.1002/anie.201801378. Epub 2018 Apr 14.
Prodrug activation, by exogenously administered enzymes, for cancer therapy is an approach to achieve better selectivity and less systemic toxicity than conventional chemotherapy. However, the short half-lives of the activating enzymes in the bloodstream has limited its success. Demonstrated here is that a tyrosinase-MOF nanoreactor activates the prodrug paracetamol in cancer cells in a long-lasting manner. By generating reactive oxygen species (ROS) and depleting glutathione (GSH), the product of the enzymatic conversion of paracetamol is toxic to drug-resistant cancer cells. Tyrosinase-MOF nanoreactors cause significant cell death in the presence of paracetamol for up to three days after being internalized by cells, while free enzymes totally lose activity in a few hours. Thus, enzyme-MOF nanocomposites are envisioned to be novel persistent platforms for various biomedical applications.
前药激活，通过外源性给予的酶，用于癌症治疗是一种比传统化疗具有更好的选择性和更低的全身毒性的方法。然而，在血液中激活酶的半衰期短限制了它的成功。本文证明，酪氨酸酶-金属有机框架纳米反应器以持久的方式在癌细胞中激活前药扑热息痛。通过产生活性氧（ROS）和消耗谷胱甘肽（GSH），扑热息痛酶转化的产物对耐药性癌细胞有毒。在被细胞内化后，即使有扑热息痛存在，酪氨酸酶-MOF 纳米反应器也能在三天内导致显著的细胞死亡，而游离酶在几个小时内完全失去活性。因此，酶-金属有机框架纳米复合材料有望成为各种生物医学应用的新型持久平台。
