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具有高特异性抑制癌细胞增殖的抗坏血酸氧化酶样纳米酶及在线电化学 DOPAC 监测。

Ascorbate oxidase-like nanozyme with high specificity for inhibition of cancer cell proliferation and online electrochemical DOPAC monitoring.

机构信息

Department of Chemistry, Capital Normal University, Beijing, 100048, China.

Department of Chemistry, Capital Normal University, Beijing, 100048, China.

出版信息

Biosens Bioelectron. 2023 Jan 15;220:114893. doi: 10.1016/j.bios.2022.114893. Epub 2022 Nov 9.

DOI:10.1016/j.bios.2022.114893
PMID:36423391
Abstract

Despite the extensive investigation of the nanozymes exhibit their favorable performance compared to natural enzymes, nevertheless, the highly specific nanozyme still needs to be developed so that it can meet the requirements of exploring the mechanism as well as administration of related diseases and selective monitoring in biological system. In this study, self-assembled glutathione-Cu/CuO nanoparticles (GSH-Cu/CuO NPs) that exhibits specific ascorbic acid (AA) oxidase-like catalytic activity were constructed for AA-activated and HO-reinforced cancer cell proliferation inhibition and selective neurochemical monitoring. Cu/CuO NPs demonstrates effective AA oxidase-like activity and no common characteristics of other redox mimic enzymes often present in nanozyme. In particular, we found that the AA oxidase-like activity of GSH-Cu/CuO nanozyme was significantly improved by about 40% by improving the activation ability toward oxygen. The synthesized nanozyme can induce the generation of active oxygen by accelerating the oxidation of AA, which effectively suppresses the proliferation of cancer cells. We constructed an online electrochemical system (OECS) though loading nanozyme with enhanced ascorbate oxidase activity into a microreactor and setting it in the upstream of the detector. This GSH-Cu/CuO NPs-integrated microreactor can completely eliminate AA interference of the physical level toward 3,4-dihydroxy phenylacetic acid (DOPAC) electrochemical measurement, and the nanozyme-based OECS is able to continuously capture DOPAC alteration in rat brain acidosis model. Our findings may inspire rational design of nanozymes with high specificity as well as nanozyme-based selectivity solution for in vivo detection and show promising opportunities for their involvement in neurochemistry investigation.

摘要

尽管纳米酶在性能上优于天然酶,已经得到了广泛的研究,但仍需要开发高度特异性的纳米酶,以满足探索机制以及相关疾病的治疗和生物系统中选择性监测的要求。在本研究中,构建了具有特定抗坏血酸(AA)氧化酶样催化活性的自组装谷胱甘肽-Cu/CuO 纳米粒子(GSH-Cu/CuO NPs),用于 AA 激活和 HO 增强的癌细胞增殖抑制和选择性神经化学监测。Cu/CuO NPs 表现出有效的 AA 氧化酶样活性,并且没有通常存在于纳米酶中的其他氧化还原模拟酶的共同特征。特别是,我们发现通过提高对氧气的激活能力,GSH-Cu/CuO 纳米酶的 AA 氧化酶样活性显著提高了约 40%。合成的纳米酶可以通过加速 AA 的氧化来诱导活性氧的产生,从而有效抑制癌细胞的增殖。我们通过将具有增强的抗坏血酸氧化酶活性的纳米酶加载到微反应器中,并将其设置在检测器的上游,构建了一个在线电化学系统(OECS)。这种 GSH-Cu/CuO NPs 集成的微反应器可以完全消除 AA 对 3,4-二羟基苯乙酸(DOPAC)电化学测量的物理水平干扰,并且基于纳米酶的 OECS 能够连续捕获大鼠脑酸中毒模型中 DOPAC 的变化。我们的研究结果可能为具有高特异性的纳米酶的合理设计以及基于纳米酶的选择性解决方案用于体内检测提供启示,并为它们在神经化学研究中的应用提供了有前途的机会。

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