血红素加氧酶
光动力疗法
抗氧化剂
谷胱甘肽
癌细胞
原卟啉IX
氧化应激
丁硫胺
化学
血红素
药理学
活性氧
生物化学
细胞生物学
癌症
生物
酶
有机化学
遗传学
作者
Hao Zhong,Peiying Huang,Ping Yan,Peiling Chen,Qun‐Yin Shi,Zean Zhao,Jing‐Xuan Chen,Xian Shu,Ping Wang,Bin Yang,Zhengzheng Zhou,Jianjun Chen,Jianxin Pang,Yingfeng Tu,Li‐Han Liu,Xian‐Zheng Zhang
标识
DOI:10.1002/adhm.202100770
摘要
Abstract The antioxidant defense system in malignant cells, which involves antioxidant enzymes and antioxidant molecules, is an innate barrier to photodynamic therapy (PDT). Because of the complexity of the endogenous antioxidant mechanisms of these cells, simply inhibiting individual antioxidant pathways has a limited effect on improving the lethality of ROS. To enhance the efficacy of PDT for tumor treatment, a versatile nanoparticle (NP)‐based drug is developed, which the authors call PZB NP, containing the glutathione inhibitor l ‐buthionine sulfoximine (BSO) and the heme oxygenase 1 (HO‐1) inhibitor protoporphyrin zinc(II) (ZnPP) to suppress the innate antioxidant defense system of cancer cells in a two‐pronged manner. BSO reduces intracellular glutathione levels to minimize ROS elimination and protein protection during PDT, and ZnPP inhibits the ROS‐stimulated upregulation of the antioxidant HO‐1, thus preventing ROS removal by cells after PDT. Thus, BSO and ZnPP synergistically suppress the antioxidant defense systems of cancer cells both during and after protoporphyrin‐IX‐mediated PDT in a two‐pronged manner, resulting in tumor cell death through excess oxidative pressure. The results demonstrate that the construction of nanodrugs having dual antioxidation defense suppression properties is a promising route for the development of highly efficient ROS‐based therapies.
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