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

摘要

To translate uPAR-targeted human ATF-IONPs into clinical applications, we evaluated MRI changes from Pre-to Post-17 days, serum iron concentrations at from Post- 5 mins to 12wks, routine blood examination and serum chemistry analyses from pre- to 12wks after administration, and stained with hematoxylin-eosin (HE) and Perls' Prussian blue of the liver at post-24 hours and 3 months in rhesus monkeys respectively injected with human ATF-IONPs with and without PEG coating. It is proved that systemic delivery of 5 mg/Kg of iron equivalent concentration of uPAR-targeted human ATF-INOPs is safe. And there were transient alterations in all of the observed variables, and were self-healing in next three months. 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.