Recombinant epidermal growth factor-like domain-1 from coagulation factor VII functionalized iron oxide nanoparticles for targeted glioma magnetic resonance imaging

Heng Liu,1,2 Xiao Chen,1 Wei Xue,1 Chengchao Chu,2 Yu Liu,2 Haipeng Tong,1 Xuesong Du,1 Tian Xie,1 Gang Liu,2 Weiguo Zhang1,3 1Department of Radiology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 2State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, Fujian, 3Chongqing Clinical Research Center for Imaging and Nuclear Medicine, Chongqing, People’s Republic of China Abstract: The highly infiltrative and invasive nature of glioma cells often leads to blurred tumor margins, resulting in incomplete tumor resection and tumor recurrence. Accurate detection and precise delineation of glioma help in preoperative delineation, surgical planning and survival prediction. In this study, recombinant epidermal growth factor-like domain-1, derived from human coagulation factor VII, was conjugated to iron oxide nanoparticles (IONPs) for targeted glioma magnetic resonance (MR) imaging. The synthesized EGF1-EGFP-IONPs exhibited excellent targeting ability toward tissue factor (TF)-positive U87MG cells and human umbilical vein endothelial cells in vitro, and demonstrated persistent and efficient MR contrast enhancement up to 12 h for preclinical glioma models with high targeting specificity in vivo. They hold great potential for clinical translation and developing targeted theranostics against brain glioma. Keywords: epidermal growth factor-like domain-1, tissue factor, iron oxide nanoparticles, MRI, glioma