International Journal of Nanomedicine (Jul 2017)
A synthetic urinary probe–coated nanoparticles sensitive to fibroblast activation protein α for solid tumor diagnosis
Abstract
Xinwei Feng,1,* Qifan Wang,1,* Yuehua Liao,1 Xie Zhou,2 Yidan Wang,3 Wanli Liu,4 Ge Zhang1 1Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 2Department of Medical Chemistry, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 3Department of Biotechnology, School of Life Science, Sun Yat-sen University, Guangzhou, 4Department of Clinical Laboratory Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China *These authors contributed equally to this work Abstract: We developed fibroblast activation protein α (FAPα)-sensitive magnetic iron oxide nanoparticles (MNPs) by conjugating a substrate-reporter tandem peptide as a synthetic biomarker to the surface of MNPs (marker-MNPs). In vitro, the marker-MNPs showed stability when treated with serum or urine and exhibited high susceptibility and specificity for FAPα enzyme and 3T3/FAPα cell line. Furthermore, the marker-MNPs were administered to esophageal squamous cell carcinoma xenograft tumor mice; they reached the tumor tissues in the mice, where they were cleaved effectively by the local overexpressed FAPα to release the reporter peptide and filter it into the urine. The tumor targeting and biodistribution of marker-MNPs were verified by in vivo imaging. The cleaved reporter peptides in urine detected by enzyme-linked immunosorbent assay have high diagnostic accuracy for esophageal squamous cell carcinoma (area under the receiver-operating characteristic curve =1.0). Our study implies a promising strategy of utilizing the low-cost and noninvasive synthetic urinary probe–coated nanoparticles for the diagnosis of FAPα-positive solid tumors, except for in renal cancer. Keywords: synthetic urinary probe, magnetic iron oxide nanoparticles, fibroblast activation protein α, tumor diagnosis
