Chronic liver conditions like hepatitis, liver cirrhosis, and hepatocellular carcinoma are significant global health concerns, causing widespread morbidity and mortality. A critical factor in these diseases is liver fibrosis, characterized by thickening and scarring of connective tissue. However, fibrosis detection is typically reliant on biopsy, which has several drawbacks, including the risk of complications, limited sampling scope, and its invasive nature, which precludes regular monitoring of disease progression. Consequently, researchers are turning to non-invasive magnetic resonance imaging (MRI) methods to detect and measure liver fibrosis across the entire organ. This advancement would facilitate earlier diagnosis and ongoing tracking of both disease progression and treatment efficacy.

Enhancing MRI for chronic conditions like fibrosis requires the creation of tissue-specific MRI contrast agents that can specifically target diseased tissue, including the collagen that accumulates in fibrotic liver. Designing these agents poses a challenge: they must effectively target and bind to the specific tissue, generate a strong MRI signal, and be rapidly eliminated from the body to minimize toxicity. A recent study, supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB, Bethesda, MD, USA) and involving collaboration across several institutions, has led to the development of a nanoparticle-based contrast agent suitable for the targeted MRI diagnosis of liver fibrosis.

This new contrast agent, termed single nanometer iron oxide collagen-binding peptide (SNIO-CBP), is composed of two functional elements. The SNIO component is a minuscule iron oxide molecule providing high MRI contrast. The CBP component targets and binds to collagen present in fibrotic liver tissue. The nanoparticle's small size enables it to leave the bloodstream and penetrate tissues, where CBP attaches to collagen in fibrotic liver, thereby avoiding attachment to healthy tissues. The iron oxide alters the magnetic properties of nearby protons, generating a strong signal that enhances MRI imaging.

The efficacy of SNIO-CBP was tested in two mouse models that replicate human liver fibrosis caused by toxins and diet. The results were highly promising, with SNIO-CBP delivering robust, collagen-specific imaging in both fibrosis models. Remarkably, the imaging was achievable just 15 minutes after injection, a significant improvement over similar experimental agents that require hours or days to accumulate in target tissues and produce an MRI image, which limits their practical clinical application. SNIO-CBP also exhibited desirable characteristics, including low signal interference in surrounding normal liver tissue and quick renal elimination. This rapid clearance reduces potential toxicity, an important consideration for patients with liver or kidney diseases.

“This work addresses an unmet clinical need for a non-invasive diagnostic to detect fibrosis that develops in a number of liver disorders,” explained Guoying Liu, Ph.D., director of the program in magnetic resonance imaging at the NIBIB. “The team has engineered a compound that meets the exacting specifications needed to accelerate potential use of this type of imaging agent in the clinic.”

“This compound successfully combines superior magnetic characteristics needed for a strong MRI signal with rapid, specific accumulation in the target tissue,” added Moungi G. Bawendi, Ph.D., at the MIT who led the research team. “We now have a molecular platform for synthesizing tissue-specific MRI contrast agents, which is a major step toward adding a highly valuable non-invasive diagnostic tool for chronic liver disease that will be applicable to a wide range of other diseases, as well.”

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