Enzyme-Mimetic Antioxidant Luminescent Nanoparticles for Highly Sensitive Hydrogen Peroxide Biosensing

Abstract

Hydrogen peroxide (H 2 O 2 ) is an abundant molecule associated with biological functions and reacts with natural enzymes, such as catalase. Even though direct H 2 O 2 measurement can be used to diagnose pathological conditions, such as infection and inflammation, H 2 O 2 quantification further enables the detection of disease biomarkers in enzyme-linked assays ( e.g., ELISA) in which enzymatic reactions may generate or consume H 2 O 2 . Such a quantification is often measured optically with organic dyes in biological media that suffer, however, from poor stability. Currently, the optical H 2 O 2 biosensing without organic-dyes in biological media and at low, submicromolar, concentrations has yet to be achieved. Herein, we rationally design biomimetic artificial enzymes based on antioxidant CeO 2 nanoparticles that become luminescent upon their Eu 3+ doping. We vary systematically their diameter from 4 to 16 nm and study their catalase-mimetic antioxidant activity, manifested as catalytic H 2 O 2 decomposition in aqueous solutions, revealing a strong nanoparticle surface area dependency. The interaction with H 2 O 2 influences distinctly the particle luminescence rendering them highly sensitive H 2 O 2 biosensors down to 0.15 μM (5.2 ppb) in solutions for biological assays. Our results link two, so far, unrelated research domains, the CeO 2 nanoparticle antioxidant activity and luminescence by rare-earth doping. When these enzyme-mimetic nanoparticles are coupled with alcohol oxidase, biosensing can be extended to ethanol exemplifying how their detection potential can be broadened to additional biologically relevant metabolites. The enzyme-mimetic nanomaterial developed here could serve as a starting point of sophisticated in vitro assays toward the highly sensitive detection of disease biomarkers.