4.8 Article

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

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BIOSENSORS & BIOELECTRONICS
卷 220, 期 -, 页码 -

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ELSEVIER ADVANCED TECHNOLOGY
DOI: 10.1016/j.bios.2022.114893

关键词

Specificity; Nanozyme; Modification; Ascorbate; DOPAC; In vivo online electrochemical detection

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Despite the favorable performance of nanozymes compared to natural enzymes, the development of highly specific nanozymes is still necessary to meet the requirements of exploring disease mechanisms and selective monitoring in biological systems. In this study, self-assembled GSH-Cu/Cu2O NPs with specific AA oxidase-like catalytic activity were constructed for cancer cell proliferation inhibition and neurochemical monitoring. The nanozyme exhibited improved activity through the generation of active oxygen by accelerating AA oxidation, effectively suppressing cancer cell proliferation and enabling continuous monitoring of DOPAC alterations in a rat brain acidosis model.
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 re-quirements of exploring the mechanism as well as administration of related diseases and selective monitoring in biological system. In this study, self-assembled glutathione-Cu/Cu2O nanoparticles (GSH-Cu/Cu2O NPs) that exhibits specific ascorbic acid (AA) oxidase-like catalytic activity were constructed for AA-activated and H2O2- reinforced cancer cell proliferation inhibition and selective neurochemical monitoring. Cu/Cu2O NPs demon-strates 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/Cu2O 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/Cu2O 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.

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