Scavenging Nanoreactors that Modulate Inflammation

Excessive reactive oxygen species (ROS) are crucial intermediaries in promoting degenerative states in tissues. Oxidative damage caused by excessive ROS elicits cellular apoptotic pathways. Despite extensive studies exploring oxidative stress mechanisms, little is known about the contribution of ROS to the pathogenesis of tissue degeneration.  We report for the first time on the development of an engineered nanoreactor that scavenges ROS in a dose-dependent fashion. We demonstrate that the protective effect of the engineered MnO₂ nanoreactors developed by incorporating MnO₂ nanoparticles within a collagen-matrix eliminated the inherent toxicity of MnO₂ nanoparticles and enhanced their efficacy to attenuate oxidative stress. In addition; we demonstrate the direct reactivity of MnO₂ toward peroxides and the nanoreactors efficacy to regulate oxidative stress and modulate inflammation in tissues. As a proof of concept, we assess the attenuation of excessive ROS production in a validated ex vivo organotypic intervertebral disc model of inflammation. Our results demonstrate that the unique environment of the MnO₂ nanoreactor results in the inhibition of ROS-induced apoptosis, the regulation of oxidative stress, the modulation of inflammation in tissues and the reduction of cell apoptosis without impairing cellular proliferation. Thus this resulting platform technology has applications in a broad range of inflammatory diseases.