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

• Published in: Bioactive materials Vol. 5; no. 4; pp. 758 - 767
• Main Authors: Lu, Rong, Zhang, Yuyang, Tao, Hongyue, Zhou, Lu, Li, Huidi, Chen, Tianwu, Zhang, Peng, Lu, Yao, Chen, Shuang
• Format: Journal Article
• Language: English
• Published: China Elsevier B.V 01.12.2020; KeAi Publishing; KeAi Communications Co., Ltd
• Subjects: Cartilage injury; Gadolinium; Hyaluronic acid; Magnetic resonance imaging contrast agents; Nanoparticles; Nanoparticles; Gadolinium; Cartilage injury; Magnetic resonance imaging contrast agents; Hyaluronic acid
• ISSN: 2452-199X; 2452-199X
• DOI: 10.1016/j.bioactmat.2020.05.009

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. Unique gadolinium-hyaluronic acid (Gd-HA) nanoparticles (NPs) were prepared via a facile freeze-drying method. The high longitudinal T1 relaxivity and cartilage affinity of Gd-HA NPs enabled the NPs to serve as an efficient MRI contrast agent for the detection of articular cartilage injuries. [Display omitted] •Unique gadolinium-hyaluronic acid (Gd-HA) nanoparticles (NPs) were prepared via a facile freeze-drying method.•Gd-HA NPs exhibited a greater r1 value as compared with those of bulk Gd-DTPA-HA and clinically used Gd-DTPA.•Gd-HA NPs significantly enhanced MR images of cartilage injured site after intra-articular injection in vivo.•Gd-HA NPs would not cause side effects in vivo and could be excreted from the body with urine.