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Email gaofabao@yahoo.com

All authors contributed toward data analysis, drafting, and revising the paper and agree to be accountable for all aspects of the work.

The authors report no conflicts of interest in this work.

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Research Funding:

The authors are grateful to the National Natural Science Foundation of China (81130027, 81520108014), the National “Twelfth Five-Year” Plan for Science and Technology Support (2012BAI23B08), and the National Basic Research Program of China (973 Program, 2011CB935800).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Nanoscience & Nanotechnology
  • Pharmacology & Pharmacy
  • Science & Technology - Other Topics
  • uPAR-IONP
  • nonhuman primates
  • transient harm
  • self-healing
  • IRON-OXIDE NANOPARTICLES
  • BISPHENOL-A PHARMACOKINETICS
  • IN-VIVO
  • CANCER-THERAPY
  • BREAST-CANCER
  • THERANOSTIC NANOPARTICLES
  • ZNO NANOPARTICLES
  • POTENTIAL TARGET
  • CONTRAST AGENTS
  • TOXICITY

Preclinical evaluation of a urokinase plasminogen activator receptor-targeted nanoprobe in rhesus monkeys

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Journal Title:

International Journal of Nanomedicine

Volume:

Volume 10

Publisher:

, Pages 6689-6698

Type of Work:

Article | Final Publisher PDF

Abstract:

Purpose: To translate a recombinant peptide containing the amino-terminal fragment (ATF) of urokinase plasminogen activator receptor-targeted magnetic iron oxide (IO) nanoparticles (uPAR-targeted human ATF-IONPs) into clinical applications, we conducted a pilot study to evaluate the toxicity and pharmacokinetics of this nanoparticle in normal rhesus monkeys. Methods: We assessed the changes in the following: magnetic resonance imaging (MRI) signals from pretreatment stage to 14 days posttreatment, serum iron concentrations from 5 minutes posttreatment to 12 weeks posttreatment, routine blood examination and serum chemistry analysis results from pretreatment stage to 12 weeks after administration, and results of staining of the liver with Perls’ Prussian Blue and hematoxylin–eosin at 24 hours and 3 months posttreatment in two rhesus monkeys following an intravenous administration of the targeted nanoparticles either with a polyethylene glycol (ATF-PEG-IONP) or without a PEG (ATF-IONP) coating. Results: The levels of alkaline phosphatase, alanine transaminase, and direct bilirubin in the two monkeys increased immediately after the administration of the IONPs but returned to normal within 20 days and stayed within the normal reference range 3 months after the injection. The creatinine levels of the two monkeys stayed within the normal range during the study. In addition, red blood cells, white blood cells, hemoglobin level, and platelets remained normal during the 3 months of the study. Conclusion: All of the results suggest that a transient injury in terms of normal organ functions, but no microscopic necrotic lesions, was observed at a systemic delivery dose of 5 mg/kg of iron equivalent concentration in the acute phase, and that no chronic toxicity was found 3 months after the injection. Therefore, we conclude that uPAR-targeted IONPs have the potential to be used as receptor-targeted MRI contrasts as well as theranostic agents for the detection and treatment of human cancers in future studies.

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© 2015 Chen et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-Noncommercial 3.0 Unported License (http://creativecommons.org/licenses/by-nc/3.0/).

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