Synergistic photothermal and antioxidant photo-responsive release hydrogel platform inhibits the IL-17 signaling pathway for osteoarthritis therapy.

Osteoarthritis (OA) is characterized by sterile intra-articular inflammation and progressive cartilage degeneration. Nanoparticle-based photothermal therapy (PTT) offers a promising intervention for OA therapy; however, drug-release control under photothermal conditions remains underexplored. Here, we present a Prussian blue-based, near-infrared (NIR) -responsive hydrogel (GPT) that enables multi-target therapy for OA through co-encapsulation of Prussian blue nanoparticles (PBNPs) and tannic acid (TA) within a thermosensitive agarose matrix. TA coordinates with unsaturated iron sites on PBNPs, synergistically enhancing antioxidant capacity while maintaining robust photothermal performance. Harnessing the thermal phase transition of low-melting-point agarose, GPT enables precise, temperature-dependent drug release: NIR irradiation triggers accelerated release within a mild therapeutic window, whereas drug release slowly in the absence of stimulation. Co-released TA/PBNPs rapidly scavenge excessive reactive oxygen species (ROS), delay chondrocyte senescence, and restore metabolic homeostasis. Moreover, the localized hyperthermia activates HSP70, enhancing chondroprotection under inflammatory stress. In mice model of OA, GPT/NIR treatment effectively slows disease progression. Transcriptomic profiling further reveals suppression of IL-17 signaling as a key mechanism contributing to reduced cartilage degradation. This platform synergistically combines controlled drug delivery and PTT, achieving unprecedented integration of IL-17 pathway inhibition with a photothermal-antioxidant system for OA treatment. It enables concurrent metabolic reprogramming and structural preservation, offering a novel strategy for disease-modifying OA therapy.