Platinum-Doped Ceria Based Biosensor for in Vitro and in Vivo Monitoring of Lactate during Hypoxia

Abstract

Measurements of lactate concentrations in blood and tissues are an important indication of the adequacy of tissue oxygenation and could be useful for monitoring the state and progress of a variety of diseases. This paper describes the fabrication, analytical characterization, and physiological application of an amperometric microbiosensor based on lactate oxidase and oxygen-rich platinum doped ceria (Pt-ceria) nanoparticles for monitoring lactate levels during hypoxic conditions. The Pt-ceria nanoparticles provided electrocatalytic amplification for the detection of the enzymatically produced hydrogen peroxide and acted as an internal oxygen source for the enzyme, enabling lactate monitoring in an oxygen depleted tissue. In vitro evaluation of the biosensor demonstrated high selectivity against physiological levels of ascorbic acid, a storage stability of 3 weeks, a fast response time of 6 s, and good, linear sensitivity over a wide concentration range. In vivo experiments performed by placing the biosensor in the hippocampus of anesthetized rats demonstrated the feasibility of continuous lactate monitoring over 2 h ischemia and reperfusion. The results demonstrate that Pt-ceria is a versatile material for use in implantable enzyme bioelectrodes, which may be used to assess the pathophysiology of tissue hypoxia. In addition to measurements in hypoxic conditions, the detection limit of this biosensor was low, 100 pM, and the materials used to fabricate this biosensor can be particularly useful in ultrasensitive devices for monitoring lactate levels in a variety of conditions.

Ceria Nanoparticles as Enzyme Mimetics

“…The utilization of nanoceria as oxidase under some special circumstances was also reported. Recently, nanoceria have been used for several applications either in biotic conditions or abiotic conditions, such as antioxidants, [63][64][65] capping [36] and neuroprotection agents, [66][67][68][69][70][71][72] biosensors, [23,28,73] immunoassays, [31,32,74] color indicator [27,[75][76][77][78][79] and so on.…”

“…[73] Measurement of real-time production of lactate in blood or other tissues can assess the status of hypoxia. Sardesai and co-workers [23] fabricated a kind of platinum doped ceria (Pt-ceria) nanoparticles combined with lactate oxidase (LOX) as an amperometric microbiosensor for lactate level detection under hypoxic conditions (Scheme 5). In both in vitro and in vivo experiments, this biosensor provided sufficient sensitivity for contin-uous lactate monitoring.…”

“…[110] Pt-nanoceria could enhance CAT mimetic catalytic activity, in which Pt acted as the electrochemical donator. [23] …”

“…[16] These enzyme mimetics have great value in practical applications, and therefore become a new frontier in inorganic, materials and analytical chemistry. [17][18][19] In previous studies, ceria nanoparticles (nanoceria) and nanoceria-supported materials have been reported to have multi-enzyme mimetic activities like those of superoxide oxidase, [20,21] catalase [22,23] and oxidase. [24,25] That means nanoceria have enzymatic activities to catalyze the scavenging of reactive oxygen species (ROS).…”

Cerium oxide nanoparticles: green synthesis and biological applications

“…86 Integration of the oxygen-rich CeO 2 -NPs in the enzyme-containing layer ensured operation of the biosensor in hypoxic conditions, and provided continuous, sensitive lactate monitoring. Measurements of lactate levels in blood and tissues are important indications of the state and progress of a variety of diseases.…”