We and others reported that acid oxidation of carbon rich sources generates nanoparticles with cellular protective properties in conditions including ischemia and inflammation. These studies mostly focused on the protective role of their superoxide dismutase (SOD) nanozyme activity. Unlike native SOD, harshly oxidized carbon nanoparticles (OCNPs) facilitate dismutation without transition metals and can achieve dismutation rates within an order of magnitude of native SOD. Mechanistic explanations for their catalytic activity include the role of quinones, in tandem with carboxyl and hydroxyl groups, and a strong intrinsic radical that participates in electron transfer reactions. We recently reported that particle size and broad redox potential are important parameters for in-vitro and in-vivo cellular protection; the former contributes to rapid cellular uptake and the latter encompasses multiple biologically relevant oxidation and reduction reactions. Given their broad redox potential, we explored other potential nanozyme actions. In addition to high-capacity SOD mimetic activity, our poly(ethylene glycol) (PEG)-modified, OCNPs also mediate the oxidation of NADH and reduction of cytochrome C, actions that support mitochondrial function in genetic conditions and exposure to toxins. Adding to this range of nanozyme actions, we recently discovered these particles oxidize hydrogen sulfide to polysulfides and thiosulfates, products that enhance endogenous antioxidant protectants through mechanisms including the antioxidant response elements. We demonstrate that our OCNPs protect from H₂S toxicity, an action of growing interest in conditions such as allergic and inflammation and genetic disorders, e.g., Down Syndrome. Electron Paramagnetic Resonance studies indicate that in the presence of superoxide, NADH or H₂S, the nanoparticle intrinsic radical undergoes a dramatic reduction in intensity implying an electrochemical reduction of the particle through either a 1e^- or a 2e^- process. Amide linked-PEG, added to enhance in-vivo bioavailability, reduces the intensity of the intrinsic radical and somewhat reduces the nanozyme activity, but remains highly cellular protective. Ethylenediamine blockade of quinones significantly reduces both the electrochemical activity of the particles and their oxidizing capacity supporting their catalytic role. We anticipate the range of nanozyme actions that OCNPs mediate to expand suggesting promising therapeutic applications.

Anton Liopo

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