Photoacoustic Nanoprobe Enabling In Situ Quantitative Detection of Glycosaminoglycans for Multi‐Stage Osteoarthritis Diagnosis

Osteoarthritis, featuring cartilage degeneration as a hallmark, is the leading cause of disability in structural joint disorders. Conventional imaging techniques fall short in precisely analyzing the molecular changes of the pathological processes, limiting their ability to guide timely interventions for retarding disease progression and alleviating socioeconomic burdens associated with long‐term medical care. Anionic glycosaminoglycans (GAGs) are components that are critical to cartilage extracellular matrix integrity, exhibiting progressive depletion patterns during cartilage degeneration and are thereby potential biomarkers for precise degeneration diagnosis. However, achieving quantitative in situ detection of GAGs remains challenging. Here, a polysaccharide‐polypyrrole (PS‐PPy) nanoprobe is developed to enable quantitative photoacoustic imaging of GAGs for the monitoring of multi‐stage osteoarthritis. Cationization of the polysaccharide component allows binding with GAGs by electrostatic interactions and enhancement of the colloidal stability, while the polypyrrole component imparts photoacoustic capabilities. A quantitative correlation is established between the photoacoustic intensity of PS‐PPy and the GAG content, providing accurate degenerated information in mice and human cartilage samples. Furthermore, the method achieved in situ quantification of GAGs depletion arising from multi‐stage osteoarthritis in mouse models. Collectively, this work establishes a nanoprobe‐based quantitative photoacoustic platform for molecular‐level spatiotemporal tracking of osteoarthritis staging. This non‐invasive and precise OA staging platform enables timely interventions and therapeutic monitoring with great translational value for clinically personalized OA management.