Dual-Pronged Attack: Biomimetic Multi-Functional MOFs for Rheumatoid Arthritis Therapy via Inhibiting Synovial Hyperplasia and Improving Immune Microenvironment.

Fibroblast-like synoviocytes (FLSs) and synovial macrophages (SMs) contribute significantly to the occurrence and development of rheumatoid arthritis (RA). Although therapeutic strategies targeting FLSs or SMs have achieved certain results, monotherapy often fails to effectively alleviate synovitis. By loading methotrexate (MTX) and glucose oxidase (GOx) in the zinc imidazole framework-8 (ZIF-8) and incorporating with the platinum nanoparticles (Pt NPs) and macrophage membranes, multifunctional probe mZPMG NPs were prepared. The mZPMG NPs can synergistically inhibit the abnormal proliferation of FLSs through drug therapy and starvation therapy, while eliminating excessive reactive oxygen species (ROS) and promoting the polarization of SMs toward M2-type macrophages. Oxygen generated through the ROS scavenging process can enhance the efficiency of the GOx starvation treatment. The in vivo experiments demonstrated that the clinical score of collagen-induced arthritis mice treated with the mZPMG NPs was 72.92% lower than those treated with PBS. Meanwhile, the mice in the mZPMG group exhibited obvious suppression of synovial hyperplasia, inflammatory infiltration, and cartilage erosion. Therefore, this study proposed to adopt a "dual pronged attack" strategy in inhibiting the abnormal proliferation of FLSs and reducing the abundance of SMs to achieve macrophage repolarization, which provides a promising platform for the comprehensive treatment of RA.