Glutathione-Responsive Magnetic Nanoparticles for Highly Sensitive Diagnosis of Liver Metastases

Liver metastasis (LM) occurs in various cancers, and its early and accurate diagnosis is of great importance. However, the detection of small LMs is still a great challenge because of the subtle differences between normal liver tissue and small metastases. Herein, we prepare glutathione (GSH)-responsive hyaluronic acid-coated iron oxide nanoparticles (HIONPs) for highly sensitive diagnosis of LMs through a facile one-pot method. HIONPs greatly enhance the signal of MRI in tumor metastases as T₁ contrast agent (CA), whereas they substantially decrease the signal of liver as T₂ CA as they aggregate into clusters upon the high GSH in liver. Consequently, MRI contrasted by HIONPs clearly distinguishes metastatic tumors (bright) from surrounding liver tissues (dark). HIONPs with superior LM contrasting capability and facile synthesis are very promising for clinical translation and indicate a new strategy to develop an ultrasensitive MRI CA for LM diagnosis that exploits high GSH level in the liver.