Osteoarthritis/Inflammation In Vitro Detection Using a Hyaluronate-Coated Au Nano-Contrast Probe

Osteoarthritis (OA) is a common and painful chronic joint disease that affects large joints, such as the knees, spine, hips, and shoulders. It is the most prevalent chronic joint disease in the world, with half of the world's population aged 65 or older suffering from some form. OA relates to the decomposition of hyaluronic acid (HA) in the joints, which is part of synovial fluid, and a high molecular weight physical hydrogel that lubricates the joint surfaces and reduces friction between articular cartilages with movement. Current OA diagnosis involves imaging with MRI, X-rays, and X-ray computed tomography (CT). Taking advantage of an FDA-approved treatment for OA, which includes HA injections in the knee of OA patients to reduce cartilage or bone friction, we have developed a HA-based nano-contrast agent that can detect OA and inflammation through reactive oxygen species (ROS) produced in inflamed joints, as well as hyaluronidase (HAse), as analytes of in vitro diagnosis. The presence of ROS and HAse leads to lysis of the HA coating of the nanoparticle (NP) scaffold and induces metal core aggregation (nanometer-sized), which significantly augments the CT signal. Material synthesis and detailed characterization are provided herein, along with NP stability, cell compatibility studies and in vitro studies with ROS and HAse. The NP metal clustering can be captured by several techniques, including UV–vis, TEM, and CT. The material could be administered intra-articularly into the knee of OA animals or patients in the future and be retained, similar to the FDA-approved HA, providing non-invasive OA, inflammation, or joint injury detection (e.g., elderly people, veterans, soldiers, and sports athletes) through X-rays or CT.