Nanonitrator: novel enhancer of inorganic nitrate’s protective effects, predicated on deep learning approach

Abstract

Inorganic nitrate is an indispensable nutrient, which has been used in experimental studies on the prevention and treatment of several diseases. However, its short half-life limits inorganic nitrate’s clinical application. To increase nitrate’s usability and overcome the challenges of traditional combination drug discovery through large-scale high-throughput biological experiments, we developed our deep learning–based combination drug prediction system, which identified vitamin C as the drug of choice to be combined with nitrate. Employing microencapsulation technology, we used vitamin C, sodium nitrate, and chitosan 3000 as the core material to prepare a nitrate nanoparticle, which we named Nanonitrator. The long-circulating delivery of nitrate by Nanonitrator significantly increased the efficacy and effect duration of nitrate in two animal models of injury, without compromising safety. Moreover, Nanonitrator at the same dose could better maintain intracellular homeostasis than nitrate (with or without vitamin C), emphasizing its potential for clinical use. More importantly, our work provides a method for the incorporation of inorganic compounds into sustained-release nanoparticles.