Nanomaterial-enabled rheumatoid arthritis treatment: An advanced investigation into photonic - acoustic - gaseous multimodal therapy.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Current treatments mainly involve drugs and surgery, but face limitations like adverse effects, invasive complications, and poor outcomes. Emerging nanomaterial-mediated modalities, particularly photothermal therapy (PTT), photodynamic therapy (PDT), photoacoustic (PA) imaging, sonodynamic therapy (SDT), and gas therapy, have demonstrated the potential to address these limitations. PTT leverages near-infrared (NIR)-responsive nanomaterials to induce localised hyperthermia, triggering apoptosis in pathogenic synovial tissues. PDT relies on photoactivated nanophotosensitizers to precisely eliminate hyperplastic synovium through spatiotemporally controlled reactive oxygen species (ROS) production. PA imaging uses NIR light to excite nanoparticles, generating ultrasound signals that are reconstructed into images, enabling real-time monitoring and assessment of RA joints. SDT employs ultrasound-activated nanosensitizers to produce cytotoxic ROS for the targeted ablation of inflammatory cells. Complementing these approaches, gas therapy, mediated by hydrogen-releasing nanomaterials, exerts immunomodulatory effects by scavenging ROS and regulating the inflammatory microenvironment. This review examines cutting-edge nanotherapeutic strategies that integrate photonic, acoustic, and gaseous modalities for RA management. Through an analysis of innovative nanosystem designs and their therapeutic mechanisms, this review highlights the emerging paradigm of synergistic multimodality approaches, which improve efficacy while reducing systemic adverse effects. This review will provide novel perspectives for advancing next-generation multimodal precision therapies for autoimmune diseases.