Gadolinium-Labeled Ferritin Nanoparticles as T1 Contrast Agents for Magnetic Resonance Imaging of Tumors

Recombinant human heavy chain (H-chain) ferritin (HFn) with gadolinium labeling (HFn-Gd) was designed as a targeted T1 contrast agent for magnetic resonance imaging (MRI) to enhance MRI efficiency in diagnosing tumors at a low dosage. The HFn-Gd nanoparticle shows a larger hydrodynamic diameter (13.6 nm) as compared to HFn (12.5 nm), and a decreased zeta potential value (-14.3 mv) as compared to HFn (-6.2 mv). Fourier transform infrared spectroscopy characterization and X-ray photoelectron spectroscopy analysis indicate the conjugation of Gd on HFn nanoparticles. Compared with Gd-DTPA (DTPA, diethylenetriaminepentaacetic acid), the HFn-Gd nanoparticle has a high r(1) value of 4.78 mM(-1) s(-1), showing good biocompatibility, stability, and active targeting ability to TfR1-positive cancer cells as revealed by cell viability tests, arsenazo III colorimetric assays, and laser scanning confocal microscopy examinations. The MRI of CFPAC-1 tumors using HFn-Gd nanoparticles (dose = 0.016 mmol Gd/kg body weight) shows an enhanced signal up to 30 min postinjection, which is significantly longer than that of Gd-DTPA (approximately 10 min). At such a low dose, the MRI of microscopic MDA-MB-231 tumors, with HFn-Gd nanoparticles, shows a significant signal change up to 60 min, while almost no detectable signal change occurs with Gd-DTPA. Furthermore, MRI reveals that HFn-Gd nanoparticles are mostly cleared through the renal system. Our results demonstrate that the HFn protein-based contrast agent integrates T-1 signal enhancing, precise tumor targeting, and systematic clearance capabilities. It is an effective T-1 contrast agent for MR imaging of tumors with a single low-dose injection.