The application of nanoparticles as diagnostic and therapeutic agents has been of great interest over the last few decades. Understanding the diffusion of nanoparticles in biological environments is critical in their design and eventual clinical application. However, there is incomplete understanding of nanoparticle diffusion in synovial fluid, the fluid inside the joint, which consists of a mixture of the polyelectrolyte hyaluronic acid, proteins, and other components.

University of Florida professors Carlos M. Rinaldi-Ramos and Kyle D. Allen, from the Department of Chemical Engineering and the J. Crayton Pruitt Family Department of Biomedical Engineering, are investigating the application of nanoparticles as diagnostic and therapeutic agents for joint diseases, such as osteoarthritis. In a recent study published in Science Advances, their research provides new insight into the diffusion of nanoparticles in synovial fluid and their analogues through application of state-of-the-art instrumentation to measure the translational and rotational motion of these tiny materials in complex biological fluid environments.

The study, led by recent graduate Mythreyi Unni, Ph.D., (Ph.D. ChE ‘19) is the first to report faster than expected nanoparticle translational and rotational diffusion in synovial fluid and in concentrated solutions of the polyelectrolyte hyaluronic acid, one of the principal components in synovial fluid. To achieve this, the team leveraged instrumentation at UF to measure nanoparticle rotational diffusion and at the Advanced Photon Source (APS), a U.S. Department of Energy User Facility at DOE’s Argonne National Laboratory, to measure nanoparticle translational diffusion. The study was conducted in collaboration with scientists from Argonne and Poland’s AGH University of Science and Technology.

“Our results suggest that polyethylene glycol (PEG) coated nanoparticles should be able to rapidly diffuse throughout the synovial fluid, potentially reaching targets such as cartilage, synovium, and the cells within those tissues,” said Mythreyi Unni, Ph.D., first author of the paper.

Unni is a Ph.D. alumna in the Rinaldi-Ramos Research Laboratory lead by the UF Department of Chemical Engineering Chair and Dean’s Leadership Professor, Carlos M. Rinaldi-Ramos, Ph.D. The Rinaldi-Ramos Research Laboratory investigates biomedical applications of magnetic nanoparticles, and the stability and transport of nanoparticles in complex and biological fluids.

The work was performed using the ultrabright X-rays at the APS. UF students visited the APS several times over a period of two years to measure nanoparticle translational diffusion using a technique called x-ray photon correlation spectroscopy.

“Recent advances in ultrafast x-ray detectors and enhancements in coherence of the x-rays have enabled probing dynamics in biological systems, which paves the way for many such scientific breakthroughs,” said Suresh Narayanan, Ph.D., of Argonne, a co-author in the study.

“Although these findings are exciting, this is only the beginning. Future studies will provide insight into the role of nanoparticle properties, such as size and charge, and joint disease state, which affects the composition of synovial fluid, on nanoparticle diffusion. We expect that the knowledge gained through these studies will help design next generation nanoparticle drug carriers to treat joint diseases,” said Dr. Carlos M. Rinaldi-Ramos, the senior corresponding author in the study.