Iron Oxide Nanoparticles for Hepatocyte-Targeted T2 Imaging with Inverse Illumination of Liver Tumors
Wang Qian, Ruiyang Suo, Yixin Liu, Zixun Zhang, Shuqi Li, Minghui Ma, Huan Ling, Jingjing Wang, Di Qiu, Jun Zhou, Bo Wu, Yongchang WeiAbstract
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.