An enhanced nanoenzyme for remodeling the inflammatory microenvironment and low-temperature photothermal cascade therapy for rheumatoid arthritis

A multi-functional nanoprobe manganese carbonyl@platinum@zinc ion-coordinated polydopamine-hyaluronic acid (MPZH) was designed to remodel the inflammatory microenvironment and low-temperature photothermal cascade therapy for rheumatoid arthritis. We found that Zn 2+ contained in MPZH significantly increased the superoxide dismutase activity of polydopamine after forming a zinc ion-coordinated polydopamine complex with polydopamine. DFT theoretical calculations revealed that the energy required for the degradation of superoxide anion to hydrogen peroxide by zinc ion-coordinated polydopamine was reduced by 3.94 eV compared with polydopamine. MPZH stimulated macrophage polarization toward the M2 phenotype by removing large amounts of reactive oxygen species from the joints and reduced the secretion of pro-inflammatory factors and downregulated the NF-κB inflammatory signaling pathway. The reaction of manganese carbonyl with hydrogen peroxide to generate carbon monoxide inhibited the overproliferation of fibroblast-like synoviocytes while significantly downregulating the expression of heat shock protein 70 and reducing the heat resistance of fibroblast-like synoviocytes. Additionally, the loaded Pt nanoparticles enhanced the photothermal conversion efficiency of zinc ion-coordinated polydopamine (45.26 %). Under this “double enhancement” effect, MPZH achieved a potent low-temperature photothermal therapy capabilities. In the mouse model of collagen-induced arthritis, MPZH demonstrated an effective inhibitory effect and excellent biocompatibility against rheumatoid arthritis. After MPZH treatment, immunofluorescence staining of joint sections revealed significantly inhibited synovial erosion. This work presents an effective strategy for mitigating rheumatoid arthritis progression and remodeling the inflammatory microenvironment.