Synergistic metabolic modulation of fibroblast-like synoviocytes <i>via</i> targeted dual prodrug nanoparticles to mitigate rheumatoid arthritis.

ABSTRACT: Elevated glucose metabolism is a prominent characteristic of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA). However, the efficacy of inhibiting a single target of glucose metabolism in FLS using small molecular inhibitors is limited for RA treatment. Herein, the synergistic inhibition of FLS' survival, proliferation, and activation by combining two glucose metabolism inhibitors, diclofenac (DC) and lonidamine (LND) was first verified. Subsequently, DC and LND were individually conjugated to cystamine-modified hyaluronic acid (HA) to prepare two polymer-prodrug conjugates. A HAP-1 peptide-modified dual polymer-prodrug conjugates-assembled nanoparticles system (^HAP-1NP_DC+LND) was further tailored in the optimal synergistic ratio for targeted and synerg

SUBMITTER: Li S 

PROVIDER: S-EPMC11873624 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature