In Vivo Electrochemical Detection of Nitric Oxide in Tumor-Bearing Mice
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文摘
Interest in elucidating the mechanisms of action of variousclasses of anticancer agents and exploring the pathwaysof the induced-nitric oxide (NO) release provides animpetus to conceive a better designed approach to locallydetect NO in tumors, in vivo. We report here on the firstuse of an electrochemical sensor that allows the in vivodetection of NO in tumor-bearing mice. In a first step, weperformed the electrochemical characterization of a stableelectroactive probe, K4Fe(CN)6, directly injected into theliquid microenvironment especially created around theelectrode in the tumor. Second, the ability of the insertedelectrode system to detect the presence of NO itself in thetumoral tissue was achieved by using the chemicallymodified Pt/Ir electrode as NO sensor and two NO donormolecules: diethylammonium (Z)-1-(N,N-diethylamino)diazen-1-ium 1,2-diolate (DEA-NONOate) and (Z)-1-[N-(2-aminopropyl)-N-(2-ammonio propyl)amino]diazen-1-ium 1,2-diolate (PAPA-NONOate). These two NO donormolecules allowed proving the electrochemical detectionof (i) directly injected exogenous NO phosphate buffersolution into the tumor (decomposed DEA-NONOate) and(ii) biomimetically induced endogeneous release of NOin the tumoral tissue, upon injection of PAPA-NONOateinto the tumor. This approach could be applied to the invivo study of candidate anticancer drugs acting on the NOpathways.

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