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

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.

In this study, we present Fe₃O₄@HFn, an ultrasensitive MRI contrast agent composed of human ferritin (HFn) encapsulating iron oxide nanoparticles. Fe₃O₄@HFn enables dual-mode longitudinal relaxation time (T₁) and transverse relaxation time (T₂) 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, Fe₃O₄@HFn exhibits 1.56-fold and 40.1-fold higher longitudinal relaxation rate (r₁ = 5.20 s^-1mM^-1) and transverse relaxation rate (r₂ = 147.6 s^-1mM^-1), respectively. At 11.7 T, it maintains superior relaxation rates (r₁ = 0.85 s^-1mM^-1, r₂ = 178.0 s^-1mM^-1). Mechanistic studies demonstrated efficient tumor targeting via TfR1 receptor-mediated endocytosis in U87 glioma and HL60 leukemia cells. In vivo, Fe₃O₄@HFn exhibited high selectivity, excellent biocompatibility, and promising potential for early cancer detection and therapeutic monitoring.

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.