Wei Zhiwei, Peng Gege, Zhao Yaqi, Chen Shengqiu, Wang Rui, Mao Hui, Xie Yi, Zhao Changsheng
State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China.
Shandong Laboratory of Yantai Advanced Materials and Green Manufacturing, Yantai 264000, China.
ACS Nano. 2022 Nov 22;16(11):18329-18343. doi: 10.1021/acsnano.2c06186. Epub 2022 Nov 10.
Oxidative stress is a compelling risk factor in chronic kidney diseases and is further aggravated for individuals during extracorporeal blood purification, ultimately leading to multiple complications. Herein, antioxidative cascade metal-phenolic nanozymes (metal-tannic acid nanozymes, M-TA NMs) are synthesized metal ions-mediated oxidative coupling of polyphenols; then M-TA NMs engineered hemoperfusion microspheres (Cu-TAn@PMS) are constructed for alleviating oxidative stress. M-TA NMs show adjustable broad-spectrum antioxidative activities toward multiple reactive nitrogen and oxygen species (RNOS) due to the adjustable catalytic active centers. Importantly, M-TA NMs could mimic the cascade processes of superoxide dismutase and catalase to maintain intracellular redox balance. Detailed structural and spectral analyses reveal that the existence of a transition metal could decrease the electronic energy band gaps of M-TA NMs to offer better electron transfers for RNOS scavenging. Notably, dynamic blood experiments demonstrate that Cu-TAn@PMS could serve as an antioxidant defense system for blood in hemoperfusion to scavenge intracellular reactive oxygen species (ROS) effectively even in the complex blood environment and further protect endogenous antioxidative enzymes and molecules. In general, this work developed antioxidative cascade nanozymes engineered microspheres with excellent therapeutic efficacy for the treatment of oxidative stress-related diseases, which exhibited potential for clinical blood purification and extended the biomedical applications of nanozymes.
氧化应激是慢性肾脏病中一个引人关注的风险因素，在体外血液净化过程中，个体的氧化应激会进一步加剧，最终导致多种并发症。在此，通过金属离子介导的多酚氧化偶联反应合成了具有抗氧化级联反应的金属-酚类纳米酶（金属-单宁酸纳米酶，M-TA NMs）；然后构建了用于减轻氧化应激的M-TA NMs工程化血液灌流微球（Cu-TAn@PMS）。由于催化活性中心可调，M-TA NMs对多种活性氮和氧物种（RNOS）表现出可调的广谱抗氧化活性。重要的是，M-TA NMs可以模拟超氧化物歧化酶和过氧化氢酶的级联过程，以维持细胞内的氧化还原平衡。详细的结构和光谱分析表明，过渡金属的存在可以降低M-TA NMs的电子能带隙，为清除RNOS提供更好的电子转移。值得注意的是，动态血液实验表明，即使在复杂的血液环境中，Cu-TAn@PMS也可以作为血液灌流中血液的抗氧化防御系统，有效清除细胞内活性氧（ROS），进一步保护内源性抗氧化酶和分子。总的来说，这项工作开发了具有优异治疗效果的抗氧化级联纳米酶工程化微球，用于治疗氧化应激相关疾病，在临床血液净化方面展现出潜力，并扩展了纳米酶的生物医学应用。
