Neutrophil‐Mimetic, ROS Responsive, and Oxygen Generating Nanovesicles for Targeted Interventions of Refractory Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA) is the most prevalent inflammatory joint disease worldwide, leading to irreversible disability and even mortality. Unfortunately, current treatment regimens fail to cure RA due to low therapeutic responses and off‐target side effects. Herein, a neutrophil membrane‐cloaked, natural anti‐arthritic agent leonurine (Leo), and catalase (CAT) co‐loaded nanoliposomal system (Leo@CAT@NM‐Lipo) is constructed to remodel the hostile microenvironment for RA remission. Due to the inflammation tropism inherited from neutrophils, Leo@CAT@NM‐Lipo can target and accumulate in the inflamed joint cavity where high‐level ROS can be catalyzed into oxygen by CAT to simultaneously accelerate the drug release and alleviate hypoxia at the lesion site. Besides, the neutrophil membrane camouflaging also enhances the anti‐inflammatory potentials of Leo@CAT@NM‐Lipo by robustly absorbing pro‐arthritogenic cytokines and chemokines. Consequently, Leo@CAT@NM‐Lipo successfully alleviated paw swelling, reduced arthritis score, mitigated bone and cartilage damage, and reversed multiple organ dysfunctions in adjuvant‐induced arthritis rats (AIA) rats by synergistic effects of macrophage polarization, inflammation resolution, ROS scavenging, and hypoxia relief. Furthermore, Leo@CAT@NM‐Lipo manifested excellent biocompatibility both at the cellular and animal levels. Taken together, the study provided a neutrophil‐mimetic and ROS responsive nanoplatform for targeted RA therapy and represented a promising paradigm for the treatment of a variety of inflammation‐dominated diseases.

The Impact of Atmospheric Cadmium Exposure on Colon Cancer and the Invasiveness of Intestinal Stents in the Cancerous Colon

“…Carcinogenic metals are renowned for their capacity to induce ROS [ 38 ]. Due to resource limitations that hindered the ability to conduct direct ROS measurements, this study instead measured the activities of NOX1, SOD1, SOD2, and CAT enzymes, which are key players in the cellular anti-oxidant defense system and in oxidative stress, to indirectly illustrate changes in the production of ROS [ 39 , 40 , 41 ]. As depicted in Figure 6 , NOX1 expression levels were statistically significantly increased in the colon tumors of the CC mice when compared to their healthy counterparts (H-Cd: p < 0.05).…”