Cun Ju-E, Pan Yang, Zhang Zhuangzhuang, Lu Yao, Li Junhua, Pan Qingqing, Gao Wenxia, Luo Kui, He Bin, Pu Yuji
National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu, 610064, China.
School of Preclinical Medicine, Chengdu University, Chengdu, 610106, China.
Biomaterials. 2022 Aug;287:121687. doi: 10.1016/j.biomaterials.2022.121687. Epub 2022 Jul 19.
Reactive oxygen species (ROS)-based nanocatalytic tumor therapy is alluring owing to the capability to generate highly cytotoxic ∙OH radicals from tumoral HO. However, the antitumor efficacy is highly dependent on the radical generation efficiency and challenged by the high levels of antioxidative glutathione (GSH) in cancer cells. Herein, we report an IR-780 decorated, GSH-depleting FeO@MIL-100 (IFM) nanocomposite for photo-enhanced tumor catalytic therapy by extensive production of ∙OH, which is realized by an integration of excellent peroxidase-like activity of IFM, selective upregulation of tumoral HO by β-lapachone, and localized hyperthermia by near infrared light irradiation. IFM shows potentiated antiproliferative effect in 4T1 cancer cells by ∙OH overproduction and glutathione scavenging, inducing intracellular redox dyshomeostasis and cell death by concurrent apoptosis and ferroptosis. In vivo antitumor investigation further demonstrates photoacoustic and fluorescence imaging-guided combinational therapy with a tumor inhibition rate of 96.4%. This study provides a strategy of photo-enhanced nanocatalytic tumor therapy by tumor-specific HO amplification and hyperthermia.
基于活性氧（ROS）的纳米催化肿瘤治疗颇具吸引力，因为它能够从肿瘤内的过氧化氢（H₂O₂）生成具有高度细胞毒性的羟基自由基（∙OH）。然而，其抗肿瘤疗效高度依赖于自由基的生成效率，并且受到癌细胞中高水平抗氧化剂谷胱甘肽（GSH）的挑战。在此，我们报道了一种用IR-780修饰的、消耗GSH的FeO@MIL-100（IFM）纳米复合材料，用于通过大量产生∙OH来实现光增强肿瘤催化治疗，这是通过IFM优异的类过氧化物酶活性、β-拉帕醌对肿瘤内H₂O₂的选择性上调以及近红外光照射引起的局部热疗相结合来实现的。IFM通过过量产生∙OH和清除谷胱甘肽，在4T1癌细胞中显示出增强的抗增殖作用，通过同时发生的凋亡和铁死亡诱导细胞内氧化还原稳态失衡和细胞死亡。体内抗肿瘤研究进一步证明了光声和荧光成像引导的联合治疗，肿瘤抑制率为96.4%。本研究提供了一种通过肿瘤特异性H₂O₂放大和热疗实现光增强纳米催化肿瘤治疗的策略。
