Photothermal reprogramming of synovial M1 macrophages reshapes the pro-inflammatory microenvironment to reverse...

Temporomandibular joint osteoarthritis (TMJOA) involves progressive synovial inflammation-driven cartilage degeneration. While thermotherapy empirically alleviates symptoms, its immunomodulatory mechanism remains elucidated. Here, we revealed that targeted mild hyperthermia reprogramed synovial M1 macrophages via NF-κB pathway suppression, shifting their secretome to attenuate chondrocyte catabolism while enhancing anabolism. This thermally-modified macrophage conditioned medium concurrently promoted osteogenic mineralization. Capitalizing on this, we engineered folic acid-conjugated Y8 nanocomposites (FA-Y8 NPs) for precision M1-targeting photothermal therapy. Under 808 nm irradiation, FA-Y8 NPs achieved localized photothermal reprogramming of synovial M1 macrophages and attenuating cartilage degradation in CFA-induced TMJOA mice. This study reveals thermal immunomodulation of synovial macrophages as a potential mechanism for TMJOA remission and establishes a targeted nanoplatform for spatial control of joint inflammation.