Ferritin-encapsulated iron oxide nanoparticles for dual-mode MRI contrast enhancement and targeted cancer imaging.

[BACKGROUND] Magnetic Resonance Imaging (MRI) is a crucial non-invasive diagnostic tool, yet its inherent contrast limitations often necessitate the use of exogenous agents. Conventional gadolinium-based contrast agents suffer from toxicity and limited specificity.

[RESULTS] In this study, we present FeO@HFn, an ultrasensitive MRI contrast agent composed of human ferritin (HFn) encapsulating iron oxide nanoparticles. FeO@HFn enables dual-mode longitudinal relaxation time (T) and transverse relaxation time (T) contrast enhancement, significantly outperforming Gd-DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), a commonly used clinical MRI contrast agent, at both 3.0 T and 11.7 T. At 3.0 T, FeO@HFn exhibits 1.56-fold and 40.1-fold higher longitudinal relaxation rate (r = 5.20 smM) and transverse relaxation rate (r = 147.6 smM), respectively. At 11.7 T, it maintains superior relaxation rates (r = 0.85 smM, r = 178.0 smM). Mechanistic studies demonstrated efficient tumor targeting via TfR1 receptor-mediated endocytosis in U87 glioma and HL60 leukemia cells. In vivo, FeO@HFn exhibited high selectivity, excellent biocompatibility, and promising potential for early cancer detection and therapeutic monitoring.

[SIGNIFICANCE] This work pioneers the integration of human ferritin nanocages with magnetic nanocores for precise, non-invasive cancer imaging, offering a transformative approach to early tumor detection and monitoring, and addressing critical safety and sensitivity limitations of existing MRI contrast agents.