pH-Responsive Cinnamaldehyde-Arginine Nanoprodrug for Targeted Rheumatoid Arthritis Therapy via Antioxidant Activity
Lihong Huang1,2, Wenlong Zhang1, Shuai Qiu1
1Department of Orthopaedics, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518033, China.
Antioxidants (Basel, Switzerland)
|May 4, 2026
Summary
A novel cinnamaldehyde-arginine nanoprodrug (Arg-CA NPs) effectively targets rheumatoid arthritis by reducing oxidative stress and inflammation. This nanoplatform shows promise for improved RA therapy with fewer side effects.
Area of Science:
- Biomaterials Science
- Nanomedicine
- Immunology
Background:
- Conventional rheumatoid arthritis (RA) treatments face challenges including poor selectivity, inadequate modulation of the inflammatory microenvironment, and systemic side effects.
- Oxidative stress and macrophage dysfunction are key targets for RA therapeutic strategies.
- Cinnamaldehyde (CA) and arginine (Arg) offer therapeutic potential but are limited by poor solubility, instability, and lack of targeted delivery.
Purpose of the Study:
- To develop a pH-responsive cinnamaldehyde-arginine nanoprodrug (Arg-CA NPs) for enhanced RA treatment.
- To evaluate the therapeutic efficacy of Arg-CA NPs in targeting oxidative stress and immune dysregulation in RA.
Main Methods:
- Synthesized pH-responsive cinnamaldehyde-arginine nanoprodrugs (Arg-CA NPs) via Schiff base reaction.
- Characterized Arg-CA NPs for solubility, stability, dispersibility, and drug release properties.
- Investigated the mechanistic effects of Arg-CA NPs on intracellular ROS, mitochondrial function, and macrophage polarization in vitro.
- Assessed the therapeutic efficacy of Arg-CA NPs in an adjuvant-induced arthritis (AIA) rat model.
Main Results:
- Arg-CA NPs demonstrated enhanced solubility, stability, and dispersibility compared to individual components.
- Arg-CA NPs effectively attenuated intracellular ROS, preserved mitochondrial function, and promoted M2 macrophage polarization by suppressing HIF-1α, COX-2, and NF-κB pathways.
- In the AIA rat model, Arg-CA NPs selectively accumulated in inflamed joints, significantly reducing swelling, synovial inflammation, cartilage erosion, and bone destruction.
Conclusions:
- Arg-CA NPs represent a promising redox-active nanoplatform for RA therapy.
- This approach effectively targets oxidative stress and macrophage-driven immune dysregulation in RA.
- Arg-CA NPs offer a potential strategy for improved RA treatment with enhanced selectivity and reduced systemic side effects.
