Scavenging Nanoreactors that Modulate Inflammation

Abstract

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. Here, the development of an engineered nanoreactor that scavenges ROS in a dose-dependent fashion is reported for the first time. It is demonstrated 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, the direct reactivity of MnO2 toward peroxides and the nanoreactors' efficacy to regulate oxidative stress and modulate inflammation in tissues are demonstrated. As a proof of concept, the attenuation of excessive ROS production in a validated ex vivo organotypic intervertebral disc model of inflammation is assessed. The results demonstrate that the unique environment of the MnO2 nanoreactor results in the inhibition of ROS-induced apoptosis, regulation of oxidative stress, modulation of inflammation in tissues, and reduction of cell apoptosis without impairing cellular proliferation. Thus, this resulting platform technology has applications in a broad range of inflammatory diseases.