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

Abstract

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.

Cationic Carrier Mediated Delivery of Anionic Contrast Agents in Low Doses Enable Enhanced Computed Tomography Imaging of Cartilage for Early Osteoarthritis Diagnosis

“…Grinstaff and colleagues developed cationic iodinated contrast agent, CA4 + with +4 net charge that exhibited 8-fold greater uptake than anionic IOX in bovine osteochondral plugs. ,,, As a result of this, 12 mg of I/mL of CA4 + showed similar CECT attenuation as from 80 mg of I/mL of anionic IOX and demonstrated strong positive correlation with GAG content. ,, In comparison, optimally charged CPC–IOX resulted in 20–50× higher intra-cartilage uptake and at low 1 mg of I/mL dose exhibited CECT attenuation similar to that of 40 mg of I/mL of IOX with strong positive correlation with GAG content. Recently, a cationic tantalum oxide nanoparticle (NP) was designed that showed high CECT correlation with cartilage GAG content but required long equilibrium time (24 h) and high NP concentration of 80 mg/mL . Use of mAv–IOX was limited by Avidin’s solubility as it started to aggregate at concentrations higher than 0.5 mg of I/mL.…”

“…Recently, a cationic tantalum oxide nanoparticle (NP) was designed that showed high CECT correlation with cartilage GAG content but required long equilibrium time (24 h) and high NP concentration of 80 mg/mL. 48 Use of mAv–IOX was limited by Avidin’s solubility as it started to aggregate at concentrations higher than 0.5 mg of I/mL. The branched PEG structure of mAv, however, offers 28 sites for IOX loading.…”

Nanoscale Contrast Agents for Ultrasound Imaging of Musculoskeletal System

“…Nanoscale contrast agents, when used in combination with imaging modalities such as CT and MRI, have been studied in preliminary applications in the musculoskeletal system. In a study by Lawson et al, CT nanoscale contrast agents enabled real-time quantitative assessment of articular cartilage, providing a comprehensive image of the disease stage [ 22 ]. Xie et al initially demonstrated a potential translational application of MRI nanoscale contrast agents in cartilage tissue engineering [ 23 ].…”