Tantalum Oxide Nanoparticles for the Quantitative Contrast-Enhanced Computed Tomography of Ex Vivo Human Cartilage: Assessment of Biochemical Composition and Biomechanics

Nanoparticle-based contrast agents, when used in concert with imaging modalities such as computed tomography (CT), enhance the visualization of tissues and boundary interfaces. However, the ability to determine the physiological state of the tissue via the quantitative assessment of biochemical or biomechanical properties remains elusive. We report the synthesis and characterization of tantalum oxide (Ta2O5) nanoparticle (NP) contrast agents for rapid, nondestructive, and quantitative contrast-enhanced computed tomography (CECT) to assess both the glycosaminoglycan (GAG) content and the biomechanical integrity of human metacarpal phalangeal joint (MCPJ) articular cartilage. Ta2O5 NPs 3-6 nm in diameter and coated with either nonionic poly(ethylene) glycol (PEG) or cationic trimethylammonium ligands readily diffuse into both healthy and osteoarthritic MCPJ cartilage. The CECT attenuation for the cationic and neutral NPs correlates with the glycosaminoglycan (GAG) content (R-2 = 0.8975, p < 0.05 and 0.7054, respectively) and the equilibrium modulus (R-2 = 0.8285, p < 0.05 and 0.9312, p < 0.05, respectively). The results highlight the importance of the surface charge and size in the design of NP agents for targeting and imaging articular cartilage. Further, nanoparticle CECT offers the visualization of both soft tissue and underlying bone unlike plain radiography, which is the standard for imaging bone in musculoskeletal diseases, and the ability to provide a real-time quantitative assessment of both hard and soft tissues to provide a comprehensive image of the disease stage, as demonstrated herein.