Oxygen-sparing photodynamic therapy via dissolving microneedles for rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent joint inflammation, which leads to significant morbidity and disability. Although current therapies offer benefits to some patients, they often fail to fully address the intricate pathophysiology of RA, particularly the inflammatory proliferation and hypoxic microenvironment in synovial tissue. Herein, we propose an oxygen-sparing photodynamic therapy (PDT) strategy via dissolving microneedles (DMNs), in which both the photosensitizer and glycolysis inhibitor are simultaneously loaded into the DMNs for RA treatment. The strategy integrates PDT to target and suppress synovial hyperplasia and alleviate joint inflammation and bone damage. Additionally, an oxygen-sparing strategy was employed through glycolysis inhibition to improve the hypoxic microenvironment in RA, thereby potentiating PDT, reducing inflammatory microenvironmental factors, and promoting inflammatory cell death. In vitro results demonstrated that the combination treatment significantly increased reactive oxygen species (ROS) levels by 426.15 %, reduced ATP content by 34.78 %, and induced significant death in inflammatory synovial cells, decreasing cell viability to 14.69 %. In adjuvant arthritis (AA) rats, the treatment significantly reduced paw swelling by 20.99 %, alleviated splenomegaly by 39.62 %, and improved inflammation and related pathological changes in both synovial and ankle tissues. Furthermore, the treatment significantly reduced serum levels of pro-inflammatory cytokines, indicating a broad anti-inflammatory effect. This multifaceted approach not only enhances therapeutic efficacy for RA but also provides a theoretical basis for the development of innovative treatment formulations.