Chitosan Nanococktails Containing Both Ceria and Superparamagnetic Iron Oxide Nanoparticles for Reactive Oxygen Species-Related Theranostics

Abstract

Reactive oxygen species (ROS) play an essential role in the progression of many chronic diseases like atherosclerosis and rheumatoid arthritis. For decades, antioxidant compounds have always been considered as potential treatments for these ROS-related diseases. Concomitantly, noninvasive imaging systems such as magnetic resonance imaging (MRI) have also been widely used in the diagnosis of diseases, especially atherosclerosis. In this study, we investigated the feasibility to develop chitosan nanococktails containing both nanoceria and superparamagnetic iron oxide nanoparticles for ROS-related theranostics. Nanoceria utilized as therapeutic modules capable of ROS scavenging and iron-oxide nanoparticles utilized as imaging agents for MRI have been synthesized separately. Subsequently, two versions of theranostic chitosan nanococktails containing both nanoceria and iron oxide nanoparticles (Chit-IOCO and Chit-TPP-IOCO) were successfully synthesized via two different mechanisms, electrostatic self-assembly, and ionic gelation. In vitro studies such as cytotoxicity, MRI, and ROS scavenging were performed. These theranostic nanococktails demonstrated effective ROS scavenging and MRI contrast as a potential platform for treatment and diagnosis of ROS-related diseases. Results indicated that both Chit-IOCO and Chit-TPP-IOCO can reduce the ROS level of the lipopolysaccharide-stimulated macrophage J774A.1 to the baseline level. Chit-IOCO was less toxic to the cells than Chit-TPP-IOCO. In addition, Chit-IOCO exhibited higher MRI relaxivity than Chi-TPP-IOCO (308 and 150 mM-1 s-1, respectively), indicating that Chi-IOCO was more effective than Chit-TPP-IOCO as an MRI contrast agent in macrophages. Taken together, Chit-IOCO nanococktail demonstrates outstanding potential for treatment and diagnosis of ROS-related diseases. Potentially, this nanococktail can be easily modified to include new modules, allowing future application of personalized medicine.