Iron Oxide Nanoparticles for Hepatocyte-Targeted T2 Imaging with Inverse Illumination of Liver Tumors

Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality worldwide, highlighting the urgent need for safe and effective imaging tools to improve early diagnosis. In this study, we developed a hepatocyte-targeted T2 MRI contrast agent by functionalizing superparamagnetic iron oxide nanoparticles (SPIONs) with an ethoxybenzyl-polyethylene glycol ligand, yielding Fe3O4-EOB-PEG2000 NPs, inspired by the hepatocyte-selective features of Gd-EOB-DTPA. In vitro studies demonstrated preferential uptake of Fe3O4-EOB-PEG2000 NPs by hepatocytes over tumor cells, while in vivo imaging in both hepatocellular carcinoma and colorectal liver metastasis models revealed a distinct "black-liver/bright-tumor" contrast effect. Compared with nontargeted Fe3O4-mPEG2000 NPs, Fe3O4-EOB-PEG2000 NPs showed significantly improved tumor visibility in T2-weighted images. Furthermore, Fe3O4-EOB-PEG2000 NPs exhibited good biocompatibility and biosafety. This work highlights a strategy for enhancing T2 MRI contrast through hepatocyte targeting, providing a promising gadolinium-free alternative for safe and effective safe and effective diagnosis of liver tumors.