Supramolecular self-assembly of EGCG–cysteine nanodrugs for ferroptosis and oxidative stress inhibition in chondrocytes to treat osteoarthritis

TL;DR

This study explores using EGCG–cysteine nanodrugs to treat osteoarthritis by inhibiting ferroptosis and oxidative stress in cartilage cells.

Contribution

A novel nanodrug based on EGCG and cysteine is developed to inhibit ferroptosis and treat osteoarthritis.

Findings

EC NPs reduced ROS, Fe2+ accumulation, and lipid peroxidation in chondrocytes.

EC NPs elevated GPX4 expression and inhibited inflammatory pathways in OA models.

In vivo tests showed EC NPs delayed OA progression in a mouse model.

Abstract

Osteoarthritis (OA) is a common chronic degenerative joint disease that is characterized mainly by the destruction of articular cartilage, synovial inflammation and osteophyte formation, and seriously affects the quality of life of middle-aged and elderly individuals. Recent studies have shown that ferroptosis plays an important role in the development of OA. The aim of this study was to utilize nanoparticles (EC NPs) formed by the self-assembly of epigallocatechin-3-gallate (EGCG) and cysteine to treat OA by inhibiting ferroptosis. The properties of the EC NPs were evaluated at the molecular level, and their therapeutic effects on H2O2-stimulated chondrocytes were verified. At the molecular level, EC NPs inhibited ROS levels, abnormal accumulation of Fe2+ and lipid peroxidation, elevated the expression of glutathione peroxidase 4 (GPX4) to inhibit ferroptosis, repaired cartilage metabolism disorders, and alleviated the progression of OA. Transcriptomic analysis further revealed that EC NPs could exert therapeutic effects by inhibiting multiple inflammatory signaling pathways. To verify their efficacy in vivo, the present study used a mouse medial meniscus instability (DMM)-induced OA model, and EC NPs were administered via intra-articular injection. The results showed that EC NPs were able to significantly attenuate damage to the cartilage matrix and delay the pathological progression of OA. In conclusion, the use of EC NPs, as a green, simple and efficient biotherapeutic strategy, is expected to provide new ideas and methods for the clinical treatment of OA.

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