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Cascade-responsive Nanobomb with domino effect for anti-tumor synergistic therapies
National Science Review ( IF 16.3 ) Pub Date : 2021-08-04 , DOI: 10.1093/nsr/nwab139
Yang Liu 1 , Yinghui Wang 1 , Shuyan Song 1 , Hongjie Zhang 1
Affiliation  

The development of reactive oxygen species (ROS) generation agents that can selectively produce sufficient ROS at the tumor site without external energy stimulation is of great significance for the further clinical application of ROS-based therapies. Herein, we designed a cascade-responsive ROS nanobomb (ZnO2@Ce6/CaP@CPPO/BSA, designated as Z@Ce6/CaP@CB) with domino effect and without external stimulation for the specific generation of multiple powerful ROS storms at the tumor site. The CaP shell and ZnO2 core gradually degrade and release Ca2+, Zn2+, and hydrogen peroxide (H2O2) under acid stimulation. On the one hand, Zn2+ can enhance the generation of endogenous superoxide anions (·O2–) and H2O2 through the inhibition of the mitochondrial electron transport chain (ETC). On the other hand, the generation of large amounts of exogenous H2O2 can cause oxidative damage to tumor cells and further activate bis[2,4,5-trichloro-6-(pentyloxycarbonyl)phenyl] oxalate (CPPO)-mediated chemiexcited photodynamic therapy. In addition, the oxidative stress caused by the generated ROS can lead to the uncontrolled accumulation of Ca2+ in cells and further result in Ca2+ overload-induced cell death. Therefore, the introduction of Z@Ce6/CaP@CB nanobombs triggered the ‘domino effect’ that caused multiple heavy ROS storms and Ca2+ overload in tumors and effectively activated anti-tumor immune response.

中文翻译:

具有多米诺效应的级联响应纳米炸弹用于抗肿瘤协同治疗

开发能够在没有外部能量刺激的情况下在肿瘤部位选择性产生足量 ROS 的活性氧 (ROS) 生成剂,对于进一步临床应用基于 ROS 的疗法具有重要意义。在此,我们设计了一种级联响应的 ROS 纳米弹(ZnO2@Ce6/CaP@CPPO/BSA,命名为 Z@Ce6/CaP@CB),具有多米诺骨牌效应,无需外部刺激,可在肿瘤处特异性产生多个强大的 ROS 风暴。地点。CaP 壳和 ZnO2 核在酸刺激下逐渐降解并释放 Ca2+、Zn2+ 和过氧化氢 (H2O2)。一方面,Zn2+可以通过抑制线粒体电子传递链(ETC)促进内源性超氧阴离子(·O2-)和H2O2的产生。另一方面,大量外源性H2O2的产生会对肿瘤细胞造成氧化损伤,并进一步激活双[2,4,5-三氯-6-(戊氧基羰基)苯基]草酸(CPPO)介导的化学激发光动力疗法。此外,产生的 ROS 引起的氧化应激会导致细胞内 Ca2+ 的不受控制的积累,进而导致 Ca2+ 超载诱导的细胞死亡。因此,Z@Ce6/CaP@CB 纳米弹的引入引发了“多米诺骨牌效应”,在肿瘤中引起多次严重的 ROS 风暴和 Ca2+ 超载,并有效激活抗肿瘤免疫反应。产生的 ROS 引起的氧化应激会导致细胞内 Ca2+ 的不受控制的积累,进而导致 Ca2+ 超载诱导的细胞死亡。因此,Z@Ce6/CaP@CB 纳米弹的引入引发了“多米诺骨牌效应”,在肿瘤中引起多次严重的 ROS 风暴和 Ca2+ 超载,并有效激活抗肿瘤免疫反应。产生的 ROS 引起的氧化应激会导致细胞内 Ca2+ 的不受控制的积累,进而导致 Ca2+ 超载诱导的细胞死亡。因此,Z@Ce6/CaP@CB 纳米弹的引入引发了“多米诺骨牌效应”,在肿瘤中引起多次严重的 ROS 风暴和 Ca2+ 超载,并有效激活抗肿瘤免疫反应。
更新日期:2021-08-04
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