Reactive Oxygen and\nNitrogen Species – “Nanosweeper”\nfor Rheumatoid Arthritis Theranostics by Macrophage Reprogramming

Excessive reactive oxygen and nitrogen species (RONS)\naccumulation\nin joints are significant variables that affect the course of rheumatoid\narthritis (RA). Scavenging of RONS to remodel macrophage homeostasis\nis a potentially powerful treatment for RA. Here, a visualized “nanosweeper”\nby functionalizing ultrasmall Gd/Fe<sub>3</sub>O<sub>4</sub> nanoparticles\nwith thiol-polyethylene glycol-phosphoric acid and 2-(3-(2-aminophenyl)ureido)\nethyl methacrylate hydrochloride (APUEMA), namely GIA NPs, can simultaneously\nscavenge both nitric oxide (NO) and reactive oxygen species (ROS),\nas well as enhance magnetic resonance imaging (MRI) for the diagnosis\nand therapy of RA. GIA NPs could not only eliminate NO by reactions\nbetween the <i>o</i>-phenylenediamine moieties of APUEMA\nand NO molecules but also remove ROS by the superoxide peroxidase\nactivities of the Fe<sub>3</sub>O<sub>4</sub> nanoparticles and thiol. <i>In vitro</i> and <i>in vivo</i> experiments revealed\nthat the simultaneous scavenging of NO and ROS strategy inhibited\nthe overactivation of the cyclic guanosine monophosphate/protein kinase\nG (cGMP/PKG) signaling pathway to reprogram the polarization states\nof macrophages and interfered with metabolism to alleviate RA. In\naddition, GIA NPs, as dual-modal nanoprobes for MRI, exhibited the\ncapacity for the early diagnosis of RA lesions and monitoring during\nthe RA treatment process. The visualized “nanosweeper”\nstrategy provides a promising integrated platform for the diagnosis\nand treatment of RA.