Accurate detection of cartilage
injuries is critical for their proper treatment because these
injuries lack the self-healing ability and lead to joint dysfunction. However, the low longitudinal T1 relaxivity (r1) and non-specificity of
contrast agents (such as
gadolinium(III)-
diethylenetriamine-pentaacetic acid (
Gd-DTPA)) significantly limit the efficiency of clinical magnetic resonance imaging (MRI) applications. To overcome these drawbacks, we integrated
hyaluronic acid (HA) with Gd to synthesize a
Gd-DTPA-HA composite, which was subsequently freeze-dried to produce nanoparticles (NPs). The resultant Gd-HA NPs demonstrated a greater r1 value (12.51 mM-1 s-1) compared with the bulk
Gd-DTPA-HA (8.37 mM-1 s-1) and clinically used
Gd-DTPA (3.88 mM-1 s-1). Moreover, the high affinity of HA to the cartilage allowed these NPs to penetrate deeper beyond the cartilage surface. As a result, Gd-HA NPs considerably increased the quality of cartilage and lesion MR images via their
intra-articular injection in vivo. Specifically, 2 h after NP administration, the signal-to-noise ratio at the injured cartilage site was 2.3 times greater than the value measured before the injection. In addition, Gd-HA NPs exhibited good biosafety properties due to the absence of adverse effects in the blood or on the main organs. It was also showed that Gd NPs were first metabolized by the kidney and liver and then excreted from the body with urine. Thus, Gd-HA NPs can potentially serve as an efficient MRI
contrast agent for improved detection of cartilage
injuries.