Nitric Oxide-Scavenging Nanogel for Treating Rheumatoid Arthritis

Abstract

Nitric oxide (NO), a radical gas molecule produced by nitric oxide synthase, plays a key role in the human body. However, when endogenous NO is overproduced by physiological disorders, severe inflammatory diseases such as rheumatoid arthritis (RA) can occur. Therefore, scavenging NO may be an alternative strategy for treating inflammatory disorders. In our previous study, we developed a NO-responsive macrosized hydrogel by incorporating a NO-cleavable cross-linker (NOCCL); here, we further evaluate the effectiveness of the NO-scavenging nanosized hydrogel (NO-Scv gel) for treating RA. NO-Scv gel is simply prepared by solution polymerization between acrylamide and NOCCL. When the NO-Scv gel is exposed to NO, NOCCL is readily cleaved by consuming the NO molecule, as demonstrated in a Griess assay. As expected, the NO-Scv gel reduces inflammation levels by scavenging NO in vitro and shows excellent biocompatibility. Furthermore, the more promising therapeutic effect of the NO-Scv gel in suppressing the onset of RA is observed in vivo in a mouse RA model when compared to the effects of dexamethasone, a commercial drug. Therefore, our findings suggest the potential of the NO-Scv gel for biomedical applications and further clinical translation.