A novel MRI contrast agent NaGdF 4 @PEG-CLS@MMP-13 NPs for detecting articular cartilage injury.

Early detection of cartilage injuries is crucial due to their limited self-repair capacity and risk of joint dysfunction. Conventional contrast agents like gadolinium-diethylenetriamine-pentaacetic acid (Gd-DTPA) offer low specificity and T1 relaxivity (r1), limiting MRI application. This study introduces NaGdF ₄ nanoparticles (NPs) modified with polyethylene glycol (PEG) and cholesterol (CLS) to enhance hydrophilicity and lipophilicity. Targeting is achieved using a matrix metalloproteinase-13 (MMP13) cartilage-binding peptide. NaGdF ₄ @PEG-CLS@MMP13 CBP NPs demonstrate an increased r1 value (8.07 mM ^-1  s ^-1 ) compared to NaGdF ₄ @PEG-CLS NPs (6.65 mM ^-1  s ^-1 ) and Gd-DTPA (3.01 mM ^-1  s ^-1 ), enabling deeper cartilage penetration and stronger cartilage affinity. Two hours post-injection, these NPs improved the signal-to-noise ratio at injury sites by 2.4-fold over pre-injection values. Biocompatibility was confirmed with no adverse effects in blood or organs, and the NPs were metabolized in kidneys and liver, with excretion via urine. This study supports NaGdF ₄ @PEG-CLS@MMP13 CBP NPs as an effective MRI contrast agent, enhancing early detection of cartilage injuries.
Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval and consent to participate: All experimental protocols were approved by the Animal Care and Use Committee of Zhejiang University. All animals received humane care according to the criteria outlined in the “Guide for the Care and Use of Laboratory Animals”. ARRIVE guidelines statement: This study adhered to the ARRIVE (Animals in Research: Reporting In Vivo Experiments) guidelines to ensure transparency and scientific rigor in the design, execution, and reporting of animal experiments. Efforts were made to minimize the number of animals used, optimize the experimental design, and implement measures to reduce animal suffering to the greatest extent possible. All animal experiments were approved by the Ethics Committee of the First Affiliated Hospital of Zhejiang University School of Medicine and conducted in strict accordance with relevant laws, regulations, and ethical standards.
(© 2025. The Author(s).)