Reactive oxygen and nitrogen species (ROS/RNS) are generated by macrophages inside their phagolysosomes. This production is essential for phagocytosis of damaged cells and pathogens, i.e., protecting our organism and maintaining immune homeostasis. The ability to quantitatively and individually monitor the four primary ROS/RNS (ONOO -, H2O2, NO, and NO2 -) with sub-millisecond resolution is clearly warranted to elucidate the still unclear mechanisms of their rapid generation and to track their concentrations variations over time inside phagolysosomes, in particular, to document the origin of ROS/RNS homeostasis during phagocytosis. A novel nanowire electrode (NWE) has been specifically developed for this purpose. It consisted of wrapping a SiC NW with a mat of 3 nm platinum nanoparticles (Pt NPs) whose high electrocatalytic performances allow the characterization and individual measurements of each of the four primary ROS/RNS. This allowed for the first time a quantitative, selective and statistically robust determination of the individual amounts of ROS/RNS present in single dormant phagolysosomes. Additionally, the sub-millisecond resolution of the nanosensor allowed confirmation and measurement of the rapid ability of phagolysosomes to differentially mobilize their enzyme pools of NADPH oxidases (NOX) and inducible nitric oxide synthases (iNOS) to finely regulate their homeostasis. This reveals an essential key to immune responses and immunotherapies and rationalizes its biomolecular origin. ASSOCIATED CONTENT Supporting InformationThe Supporting Information is available free of charge at http://pubs.acs.org.Experimental details and supplement data including characterization analysis, electrochemical measurements and cell experiments (PDF)

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In vivo, endothelial cells are permanently subjected to dynamic cyclic stretch and adapt to it through the release of vasoactive substances. Among them, reactive oxygen species (ROS) and nitric oxide (NO) are indispensable redox molecules, the contents of which and their ratio are closely implicated with endothelial redox homeostasis. However, simultaneous and quantitative monitoring of ROS and NO release in endothelial mechanotransduction remains a great challenge. Herein, a stretchable electrochemical device is developed with a dual electrode based on gold nanotubes decorated with uniform and tiny platinum nanoparticles. This hybrid nanostructure endows the sensor with high sensitivity toward both hydrogen peroxide (H 2 O 2 ) (as the most stable ROS) and NO electrooxidation. Importantly, the two species can be well discriminated by applying different potentials, which allows simultaneous monitoring of H 2 O 2 and NO release in stretch-induced endothelial mechanotransduction by the same device. The results of quantitative analysis suggest that endothelial redox homeostasis and its alteration are strongly related to vascular biomechanical and biochemical milieus. Further investigation reveals that the interplay of ROS and NO signaling has an important role in the regulation of endothelial redox state. This work will greatly facilitate the deep understanding of the molecular mechanism of endothelial dysfunction and vascular disorder.