NeutroCure goal is to develop improved drugs for an effective immune system. An over-active immune system may lead to chronic inflammation and the cytokine storm phenomenon that can be observed during infection. Our hypothesis is that resolution of inflammation is dependent on the timely production of reactive oxygen species (ROS) by the first inflammatory cell on the scene, the neutrophil, to maximize clearance of pro-inflammatory debris. We know that if ROS production is insufficient, for example when the enzyme NOX2 is absent or mutant, then inflammation persists. Central to our project is the development of new technology to resolve inflammation - novel ROS-amplifiers that are designed as single- and multiple-trigger-dependent prodrugs targeting different organelles within cells. As triggers we use elevated ROS, neutrophil elastase activity and eventually nitric oxide (NO) as well as their combinations. Two classes of prodrugs are being designed, synthesized, formulated and evaluated during the project. The first class of these acts independently of NOX2 and is based on N-alkylaminoferrocene (NAAF) and the second one is NOX2-dependent.