Abstract
Inorganic nitrate is an indispensable nutrient that has been used in experimental studies for the prevention and treatment of several diseases. However, the short half-life of nitrate limits its clinical application. To increase the usability of nitrate and overcome the challenges of traditional combination drug discovery through large-scale high-throughput biological experiments, we developed a swarm learning-based combination drug prediction system that 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 materials to prepare a nitrate nanoparticle, which we named Nanonitrator. The long-circulating delivery ability of nitrate by Nanonitrator significantly increased the efficacy and effect duration of nitrate in irradiation-induced salivary gland injury, without compromising safety. 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 incorporating inorganic compounds into sustained-release nanoparticles.