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Gadolinium-hyaluronic acid nanoparticles as an efficient and safe magnetic resonance imaging contrast agent for articular cartilage injury detection.

Abstract
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.
AuthorsRong Lu, Yuyang Zhang, Hongyue Tao, Lu Zhou, Huidi Li, Tianwu Chen, Peng Zhang, Yao Lu, Shuang Chen
JournalBioactive materials (Bioact Mater) Vol. 5 Issue 4 Pg. 758-767 (Dec 2020) ISSN: 2452-199X [Electronic] China
PMID32637740 (Publication Type: Journal Article)
Copyright© 2020 [The Author/The Authors].

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