Tracking Osteoarthritis with Nanoparticles
By Mark Dwortzan
A chronic disease afflicting more than 27 million Americans and 630 million worldwide, osteoarthritis occurs as the protective cartilage coating on joints in the knees, hips and other parts of the body degrades. No cure for osteoarthritis exists, but treatments can slow its progression, reduce pain and restore joint functioning. Now a team of researchers led by Professor Mark Grinstaff (BME, Chemistry, MSE) has developed a sensitive imaging method that promises to enhance diagnosis of osteoarthritis and enable improved care through earlier detection and more targeted treatments.
The method combines nanotechnology, engineering and medicine, and exploits new, biocompatible nanoparticles as contrast agents to image surface and interior regions of articular cartilage (the smooth, water-rich tissue that lines the ends of bones in load-bearing joints) — regions that traditional X-ray illumination cannot detect. The research, which was funded by the National Institutes of Health, is described in the June 30 issue of Angewandte Chemie.
“In the short term, these contrast agents could be used to image cartilage over time to monitor the efficacy of proposed osteoarthritis drugs,” said Grinstaff. “With continued development, they may enable clinicians to diagnose and stage the disease so that the most appropriate course of treatment could be followed.”
Two members of Grinstaff’s lab, MD/PhD student Jonathan Freedman (Pharmacology) and Postdoctoral Fellow Hrvoje Lusic (BME and Chemistry), synthesized a new nanoparticle contrast agent made of tantalum oxide that diffuses into the cartilage, thus enabling clinicians to use CT-scans to assess cartilage thickness and pinpoint lesions and injuries in osteoarthritic tissue. Guided by their clinical collaborator, Beth Israel Deaconess Medical Center/Harvard Medical School physician Brian Snyder, Freedman and Lusic used the nanoparticles to successfully image rat articular cartilage in in vivo and ex vivo experiments, as well as in a cadaverous finger joint.
They chose tantalum as a contrast agent material because it absorbs a greater fraction of X-rays produced at clinical scanning voltages than traditional materials. In addition, the tantalum nanoparticles’ positive charge automatically directs the particles to the cartilage, which carries a negative charge. Building on their initial success, the researchers plan to conduct additional in vivo experiments in animal models.
The impetus for exploring new and better contrast agents came from Snyder, who sought better ways to diagnose and assess treatment of osteoarthritis. Grinstaff sees the new method as especially promising for early detection of the disease.
“Today we have very poor capability to detect early stage osteoarthritis,” said Grinstaff. “Most patients come into the clinic at stage three when the pain becomes significant, but if diagnostics based on our method is done proactively, many patients could get the treatment they need much earlier and avoid a lot of discomfort.”