An intelligent responsive multifunctional nanoplatform for spatiotemporally programmed intervention of osteoarthritis.

Abstract

Osteoarthritis (OA) is a progressive degenerative joint disease characterized by dynamic pathological evolution. Existing therapies are largely confined to single-phase interventions and therefore fail to address the distinct biological requirements that arise during disease progression. Here, we report an intelligent responsive multifunctional nanoplatform that enables spatiotemporally programmed, stage-specific intervention of osteoarthritis through precisely controlled near-infrared (NIR) irradiation. During the initial phase, high-intensity NIR irradiation (1.5 W/cm²) preferentially eliminates pathological fibroblast-like synoviocytes through activation of an Rn7sk-associated apoptotic signaling pathway, thereby attenuating oxidative stress and inflammation-associated matrix degradation. Following microenvironmental remodeling, repeated low-intensity NIR irradiation (0.5 W/cm²) activates endogenous mesenchymal stem cells, enhances chondrogenic differentiation, and promotes extracellular matrix reconstruction, accompanied by increased expression of COL2A1, ELN, COL9A2, and COL11A2, ultimately restoring cartilage structure and function. Rather than relying on a static therapeutic modality, this programmable photothermal strategy synchronizes pathological suppression with regenerative activation according to the evolving biological requirements of osteoarthritis. Collectively, this work establishes a stage-matched therapeutic framework for precise microenvironmental regulation and provides a conceptual strategy for treating chronic degenerative diseases characterized by dynamically evolving pathological processes.