Department of Chemistry, College of Chemistry and Materials Science, Jinan University, Guangzhou, 510632, China.
Department of Chemistry, College of Chemistry and Materials Science, Jinan University, Guangzhou, 510632, China; College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China.
Biomaterials. 2020 Apr;238:119848. doi: 10.1016/j.biomaterials.2020.119848. Epub 2020 Feb 6.
The application of nanozymes to specifically treat tumors in the tumor microenvironment (TME) would be a novel and effective strategy. Here, ultra-small IrRu alloy nanoparticles (IrRu NPs) with dual enzyme activities were synthesized by a simple method. PEG surface modification was carried out to improve the biocompatibility of nanoparticles. Meanwhile, the natural enzyme glucose oxidase (GOx) was loaded to synthesize a multi-enzyme nanoreactor (IrRu-GOx@PEG NPs) that could undergo cascade catalytic reaction. In the first catalytic stage, GOx in IrRu-GOx@PEG NPs degraded tumor tissue-sensitive glucose to hydrogen peroxide (HO), which cut off the nutrient source of the tumor and inhibited tumor growth by starvation therapy. In the second catalytic stage, IrRu NPs in IrRu-GOx@PEG NPs catalyzed the upstream endogenous HO to highly toxic singlet oxygen O and O. Among them, O could directly induce apoptosis of cancer cells by the oxidative therapy, and O could resolve the problem of hypoxia that easily led to the termination of the starvation therapy response in tumor microenvironment, thereby making the cycle of starvation therapy-related reactions continue to occur. It also inhibited the metastasis of tumors caused by hypoxia. In vitro catalytic activity studies showed that IrRu-GOx@PEG NPs had good and stable catalytic activity and could effectively induce apoptosis of 4T1 cancer cells. In addition, in vivo results further demonstrated that IrRu-GOx@PEG NPs could effectively treat breast cancer in combination with starvation therapy and oxidative therapy. This treatment strategy is expected to be used in the treatment of other cancers, bringing new treatment strategies for cancer treatment.
纳米酶在肿瘤微环境（TME）中特异性治疗肿瘤将是一种新颖而有效的策略。在这里，通过一种简单的方法合成了具有双重酶活性的超小 IrRu 合金纳米粒子（IrRu NPs）。通过 PEG 表面修饰提高了纳米粒子的生物相容性。同时，负载天然酶葡萄糖氧化酶（GOx）以合成多酶纳米反应器（IrRu-GOx@PEG NPs），可以进行级联催化反应。在第一催化阶段，IrRu-GOx@PEG NPs 中的 GOx 将肿瘤组织敏感的葡萄糖降解为过氧化氢（HO），通过饥饿疗法切断肿瘤的营养来源并抑制肿瘤生长。在第二催化阶段，IrRu-GOx@PEG NPs 中的 IrRu NPs 催化上游内源性 HO 生成高毒性单线态氧 O 和 O。其中，O 通过氧化疗法直接诱导癌细胞凋亡，O 可以解决肿瘤微环境中易导致饥饿疗法反应终止的缺氧问题，从而使饥饿疗法相关反应的循环继续发生。它还抑制了由缺氧引起的肿瘤转移。体外催化活性研究表明，IrRu-GOx@PEG NPs 具有良好且稳定的催化活性，能够有效诱导 4T1 癌细胞凋亡。此外，体内结果进一步证明，IrRu-GOx@PEG NPs 可以与饥饿疗法和氧化疗法相结合有效治疗乳腺癌。这种治疗策略有望用于治疗其他癌症，为癌症治疗带来新的治疗策略。
