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Updated: Aug 22, 2026
An Adoptive Transfer Model of Rheumatoid Arthritis in Mice
Published on: June 6, 2025
M2 Macrophage-Mimetic and ROS-Sensitive Hybrid Nanoplatform for Targeted Alleviation of Rheumatoid Arthritis
Yi Xiao1, Shiyu Meng1, Zhuang Tang1
1School of Pharmacy and State Key Laboratory of Quality Research in Chinese Medicine Macau University of Science and Technology Macao China.
Abstract:
Rheumatoid arthritis (RA) constitutes the most prevalent inflammatory arthropathy globally, which is typically marked by synovitis and deteriorating joint damage. Regrettably, RA remains incurable owing to insufficient therapeutic response along with severe side reactions of available treatments. To overcome these formidable obstacles, an M2 macrophage membrane-cloaked, ROS-sensitive lipid-gated, and herbal anti-arthritic agent celastrol (Cel)-loaded hybrid silica nanosystem (Cel@M2-L-MSN) was established to reshape the intricate RA microenvironment. Benefiting from cell membrane camouflaging, Cel@M2-L-MSN inherited the inflammation-homing capability of M2 macrophages and selectively accumulated in the inflamed joints, where excessive ROS triggered Cel release from the mesopores to exert anti-inflammatory and antioxidative effects for joint protection. Moreover, Cel@M2-L-MSN demonstrated strengthened anti-inflammatory capability by robustly sponging multiple pro-arthritogenic factors including TNF-α, IL-1β, and CCL-2. In adjuvant-induced arthritis (AIA) rats, Cel@M2-L-MSN tremendously alleviated arthritis symptoms, mitigated cartilage and bone degeneration, and attenuated major organ injuries by playing multiple roles including inflammation downregulation, ROS clearance, and macrophage repolarization. Furthermore, Cel@M2-L-MSN substantially enhanced the cyto/hemocompatibility of free Cel and manifested good biosafety in vivo. Collectively, this study presents a biohybrid and stimuli-responsive nanomedicine for targeted RA remission, which also holds great promise for the clinical intervention of a wide spectrum of refractory inflammatory diseases.
Insights
A novel nanomedicine targets rheumatoid arthritis (RA) by delivering celastrol to inflamed joints, reducing inflammation and protecting against joint damage. This innovative treatment improves safety and shows promise for other inflammatory diseases.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Rheumatology
Background:
- Rheumatoid arthritis (RA) is a prevalent inflammatory disease causing joint damage, with current treatments offering limited efficacy and significant side effects.
- The complex RA microenvironment presents challenges for effective therapeutic intervention.
Purpose of the Study:
- To develop a novel hybrid silica nanosystem (Cel@M2-L-MSN) for targeted delivery of celastrol (Cel) to the RA microenvironment.
- To investigate the anti-inflammatory, antioxidative, and joint-protective effects of Cel@M2-L-MSN in a rat model of RA.
Main Methods:
- Fabrication of M2 macrophage membrane-cloaked, ROS-sensitive, lipid-gated, celastrol-loaded hybrid silica nanosystems (Cel@M2-L-MSN).
- Evaluation of targeted accumulation in inflamed joints and drug release triggered by reactive oxygen species (ROS).
- Assessment of anti-inflammatory effects by measuring pro-arthritogenic factors (TNF-α, IL-1β, CCL-2) and in vivo efficacy in adjuvant-induced arthritis (AIA) rat models.
Main Results:
- Cel@M2-L-MSN selectively accumulated in inflamed joints, with ROS triggering controlled celastrol release.
- The nanosystem demonstrated potent anti-inflammatory and antioxidative effects, significantly alleviating arthritis symptoms and mitigating cartilage/bone degeneration in AIA rats.
- Cel@M2-L-MSN exhibited improved biocompatibility and biosafety compared to free celastrol.
Conclusions:
- The developed biohybrid, stimuli-responsive nanomedicine offers a promising strategy for targeted rheumatoid arthritis remission.
- Cel@M2-L-MSN effectively reshapes the RA microenvironment, downregulates inflammation, clears ROS, and repolarizes macrophages.
- This nanomedicine holds potential for the clinical intervention of various refractory inflammatory diseases.
