A novel MRI contrast agent NaGdF₄@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 NaGdF₄ 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. NaGdF₄@PEG-CLS@MMP13 CBP NPs demonstrate an increased r1 value (8.07 mM^-1 s^-1) compared to NaGdF₄@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 NaGdF₄@PEG-CLS@MMP13 CBP NPs as an effective MRI contrast agent, enhancing early detection of cartilage injuries.