Toxicity and Pharmacokinetics of uPAR-targeted Human ATF-conjugated Iron Oxide Nanoparticles following Systemic Delivery in Rhesus Monkey

Y. Chen, J. Liao, L. Gong, H. Mao, W. Zeng, L. Yang and F. Gao
West China Hospital, Sichuan University, CN

Keywords: uPAR, rhesus monkey, MR imaging, pharmacokinetics


Increasing evidence support the potential of a novel cell surface receptor-targeted MRI nanoprobe produced by conjugating a recombinant peptide amino-terminal fragment (ATF) of urokinase plasminogen activator (uPA) to magnetic iron oxide nanoparticles (IONP) in targeted cancer imaging and therapy. To translate uPAR-targeted human ATF-IONPs into clinical applications, we examined toxicity and pharmacokinetics of uPAR-targeted human ATF-IONPs and the feasibility of non-invasive MRI follow-up of IONPs accumulation in the major organs in rhesus monkeys following systemic delivery.Systemic delivery of 5 mg/Kg of iron equivalent concentration of uPAR-targeted human ATF-INOPs has been shown to be safe in the rhesus monkey. The transient abnormality in serological test of hepatic function was also observed, suggesting that there may be a general side effect caused by uPAR-targeted human ATF-INOPs probes. But the liver function was recovery 3 month after the injection. Therefore, results of our study in monkeys support the potential of future development of uPAR-targeted IONPs as receptor-targeted MRI contrasts as well as theranostic agents for the detection and treatment of human cancers.