Early Diagnosis and Therapeutic Evaluation of Rheumatoid Arthritis by a Mitochondria-Targeted Near-Infrared Fluorescent Probe

Abstract As a chronic autoimmune inflammatory ailment, rheumatoid arthritis (RA) presents with persistent synovitis and progressive destruction of cartilage and bone structures, for which early diagnosis and real-time evaluation of therapeutic responses remain significant clinical challenges. Dysregulation of the inflammatory microenvironment, especially mitochondrial dysfunction accompanied by abnormal elevation of mitochondrial viscosity, is closely associated with RA progression. However, current imaging techniques are still insufficient for real-time visualization of these subcellular changes during disease development and treatment. Herein, we present a mitochondria-targeted near-infrared fluorescent probe, YJ-1, constructed based on a donor−π−acceptor (D−π−A) framework for sensitive detection of viscosity variations and dynamic RA imaging. YJ-1 exhibits excellent selectivity toward viscosity changes, efficient mitochondrial localization, and a strong near-infrared emission at 764 nm, enabling high-contrast and low-background imaging. Moreover, the probe demonstrates outstanding photostability, low cytotoxicity, and good biocompatibility. Owing to these advantages, YJ-1 enables real-time visualization of mitochondrial viscosity changes in living cells, zebrafish, and mouse models. In addition, in a λ-carrageenan-induced inflammatory mouse model, YJ-1 successfully monitors disease-associated mitochondrial viscosity alterations and dynamically evaluates mesenchymal stem cell (MSC)-mediated immunoregulatory therapy. Collectively, YJ-1 provides a robust imaging platform for exploring mitochondrial microenvironment dynamics during RA progression and offers a promising strategy for assessing therapeutic efficacy in inflammatory diseases.