NaGdF 4 @ PEG-CLS@ MMP-13 cartilage-binding peptide NPs as a safe and effective MRI contrast agent for articular cartilage injury

Abstract

Abstract Background The precise and early detection of cartilage injuries bears immense significance, given their innate lack of self-healing capacity and propensity to cause joint dysfunction. Regrettably, the clinically conventional contrast agents, such as gadolinium-diethylenetriamine-pentaacetic acid (Gd-DTPA) with low longitudinal T1 relaxivity (r1) and a dearth of specificity limitted the MRI applications; Methods This study focused on NaGdF4 nanoparticles (NPs), subsequently augmenting their hydrophilicity and lipophilicity via polyethylene glycol (PEG) and cholesterol (CLS) modifications.Matrix metalloproteinase-13 (MMP13) cartilage binding peptide (CBP) was harnessed to confer targeting capabilities. NaGdF4@PEG-CLS@MMP13 CBP NPs exhibited an elevated r1 value (8.07 mM − 1 s − 1) when juxtaposed with NaGdF4@PEG-CLS NPs (6.65 mM − 1 s − 1) and Gd-DTPA (3.01 mM − 1 s − 1); Results This NPs enhanced its affinity to cartilage and facilitated deeper penetration beyond the cartilage surface. Consequently, the NaGdF4@PEG-CLS@MMP13 CBP NPs instigated a notable enhancement in the quality of cartilage and lesion MR images. Specifically, a mere 2 hours following NP administration, the signal-to-noise ratio (SNR) at the injured cartilage site exhibited a remarkable 2.4-fold escalation in comparison to its pre-injection counterpart. Furthermore, the biocompatibility profile of NaGdF4@PEG-CLS@MMP13 CBP NPs proved favorable, with no observed adverse effects in blood samples or major organs; Conclusions This study demonstrated that Gd NPs underwent initial metabolism in the kidneys and liver, followed by excretion through urine. The cumulative evidence firmly positions NaGdF4@PEG-CLS@MMP13 CBP NPs as a promising and effective MRI contrast agent, poised to advance the early detection capabilities of cartilage injuries.