A ROS-responsive supramolecular peptide hydrogel attenuates rheumatoid arthritis by modulating synoviocyte activity...

Area of Science:

• Biomaterials Science
• Rheumatology
• Nanotechnology

Background:

• Rheumatoid arthritis (RA) pathogenesis involves oxidative stress, inflammation, and fibroblast-like synoviocyte (FLS) hyperactivation.
• Current therapeutic strategies for RA have limitations in simultaneously addressing these interconnected pathological processes.

Purpose of the Study:

• To develop a single-component supramolecular hydrogelator for localized RA therapy.
• To create a material that integrates anti-inflammatory drug delivery with redox-responsive properties and suppression of FLS activity.

Main Methods:

• Design and synthesis of Naproxen-Thioketal-Phe-Phe-Met(O) (NTF) hydrogelator.
• Characterization of NTF hydrogel formation, ROS-responsive disassembly, drug release kinetics, and radical-scavenging activity.
• In vitro assessment of NTF effects on RA-derived FLS and macrophages.
• In vivo evaluation of NTF hydrogel in a collagen-induced arthritis rat model.

Main Results:

• NTF spontaneously formed an injectable nanofibrous hydrogel under physiological conditions.
• The hydrogel demonstrated ROS-responsive disassembly, sustained naproxen release, and radical-scavenging properties.
• NTF inhibited FLS proliferation, migration, and invasion, reduced macrophage ROS, alleviated joint swelling, and reduced inflammation and cartilage damage in vivo.

Conclusions:

• NTF acts as an intrinsically therapeutic hydrogelator for RA.
• It effectively couples redox-responsive drug release with the suppression of pathogenic synoviocyte behavior.
• This approach offers a promising local strategy to interrupt the inflammatory microenvironment driving RA progression.