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


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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.

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Journal: TechConnect Briefs
Volume: 1, Nanotechnology 2014: Graphene, CNTs, Particles, Films & Composites
Published: June 15, 2014
Pages: 172 - 175
Industry sector: Advanced Materials & Manufacturing
Topic: Nanoparticle Synthesis & Applications
ISBN: 978-1-4822-5826-4