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Neutrophil-Mimetic, ROS Responsive, and Oxygen Generating Nanovesicles for Targeted Interventions of Refractory
Zhuang Tang1, Shiyu Meng1, Xiaoxue Yang1
1School of Pharmacy and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao, 999078, China.
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.
Insights
A novel nanoplatform using neutrophil membranes loaded with leonurine and catalase (Leo@CAT@NM-Lipo) effectively treats rheumatoid arthritis (RA) by targeting inflammation and reducing oxidative stress.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Immunology
- Rheumatology
Background:
- Rheumatoid arthritis (RA) is a global inflammatory disease causing significant disability and mortality.
- Current RA treatments have limitations including low efficacy and adverse side effects.
- The inflammatory microenvironment in RA joints presents therapeutic challenges.
Purpose of the Study:
- To develop a neutrophil membrane-cloaked nanoliposomal system co-loaded with leonurine (Leo) and catalase (CAT) for RA treatment.
- To investigate the targeted delivery and therapeutic efficacy of the Leo@CAT@NM-Lipo system in an adjuvant-induced arthritis (AIA) rat model.
- To evaluate the system's ability to remodel the RA microenvironment through ROS scavenging and hypoxia relief.
Main Methods:
- Construction of a neutrophil membrane-cloaked nanoliposomal system (Leo@CAT@NM-Lipo).
- Evaluation of the system's targeting ability and accumulation in inflamed joint tissues.
- Assessment of therapeutic effects in AIA rats, including paw swelling, arthritis scores, bone/cartilage damage, and organ function.
- Analysis of underlying mechanisms, such as macrophage polarization, inflammation resolution, ROS scavenging, and hypoxia alleviation.
Main Results:
- Leo@CAT@NM-Lipo demonstrated efficient targeting and accumulation in inflamed joints.
- The system significantly alleviated RA symptoms in AIA rats, including reduced swelling, lower arthritis scores, and mitigated tissue damage.
- Therapeutic benefits were attributed to synergistic effects including macrophage polarization, inflammation resolution, ROS scavenging, and hypoxia relief.
- Excellent biocompatibility was observed at both cellular and animal levels.
Conclusions:
- The neutrophil-mimetic, ROS-responsive nanoplatform (Leo@CAT@NM-Lipo) offers a promising strategy for targeted RA therapy.
- This approach effectively remodels the hostile RA microenvironment, leading to disease remission.
- The study presents a potential paradigm for treating various inflammation-dominated diseases.
