PMID- 26604745
OWN - NLM
STAT- MEDLINE
DCOM- 20160906
LR  - 20181202
IS  - 1178-2013 (Electronic)
IS  - 1176-9114 (Print)
IS  - 1176-9114 (Linking)
VI  - 10
DP  - 2015
TI  - Preclinical evaluation of a urokinase plasminogen activator receptor-targeted 
      nanoprobe in rhesus monkeys.
PG  - 6689-98
LID - 10.2147/IJN.S90587 [doi]
AB  - 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.
FAU - Chen, Yushu
AU  - Chen Y
AD  - Molecular Imaging Center, Department of Radiology, West China Hospital, Sichuan 
      University, Chengdu, People's Republic of China.
FAU - Gong, Li
AU  - Gong L
AD  - Sichuan Primed Bio-Tech Group Co, Ltd, Chengdu, People's Republic of China.
FAU - Gao, Ning
AU  - Gao N
AD  - Department of Radiology and Imaging Sciences, Emory University School of 
      Medicine, Atlanta, GA, USA.
FAU - Liao, Jichun
AU  - Liao J
AD  - Molecular Imaging Center, Department of Radiology, West China Hospital, Sichuan 
      University, Chengdu, People's Republic of China.
FAU - Sun, Jiayu
AU  - Sun J
AD  - Molecular Imaging Center, Department of Radiology, West China Hospital, Sichuan 
      University, Chengdu, People's Republic of China.
FAU - Wang, Yuqing
AU  - Wang Y
AD  - Molecular Imaging Center, Department of Radiology, West China Hospital, Sichuan 
      University, Chengdu, People's Republic of China.
FAU - Wang, Lei
AU  - Wang L
AD  - Molecular Imaging Center, Department of Radiology, West China Hospital, Sichuan 
      University, Chengdu, People's Republic of China.
FAU - Zhu, Pengjin
AU  - Zhu P
AD  - Molecular Imaging Center, Department of Radiology, West China Hospital, Sichuan 
      University, Chengdu, People's Republic of China.
FAU - Fan, Qing
AU  - Fan Q
AD  - Molecular Imaging Center, Department of Radiology, West China Hospital, Sichuan 
      University, Chengdu, People's Republic of China.
FAU - Wang, Yongqiang Andrew
AU  - Wang YA
AD  - Ocean NanoTech, LLC, San Diego, CA.
FAU - Zeng, Wen
AU  - Zeng W
AD  - Sichuan Primed Bio-Tech Group Co, Ltd, Chengdu, People's Republic of China.
FAU - Mao, Hui
AU  - Mao H
AD  - Department of Radiology and Imaging Sciences, Emory University School of 
      Medicine, Atlanta, GA, USA.
FAU - Yang, Lily
AU  - Yang L
AD  - Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA.
FAU - Gao, Fabao
AU  - Gao F
AD  - Molecular Imaging Center, Department of Radiology, West China Hospital, Sichuan 
      University, Chengdu, People's Republic of China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151028
PL  - New Zealand
TA  - Int J Nanomedicine
JT  - International journal of nanomedicine
JID - 101263847
RN  - 0 (Ferric Compounds)
RN  - 0 (Receptors, Urokinase Plasminogen Activator)
RN  - 1K09F3G675 (ferric oxide)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
SB  - IM
MH  - Animals
MH  - Ferric Compounds
MH  - Liver/metabolism
MH  - Macaca mulatta
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - *Molecular Targeted Therapy
MH  - Nanoparticles/*chemistry
MH  - Polyethylene Glycols/chemistry
MH  - Receptors, Urokinase Plasminogen Activator/*metabolism
MH  - Spleen/metabolism
MH  - Time Factors
PMC - PMC4630189
OTO - NOTNLM
OT  - nonhuman primates
OT  - self-healing
OT  - transient harm
OT  - uPAR-IONP
EDAT- 2015/11/26 06:00
MHDA- 2016/09/07 06:00
PMCR- 2015/10/28
CRDT- 2015/11/26 06:00
PHST- 2015/11/26 06:00 [entrez]
PHST- 2015/11/26 06:00 [pubmed]
PHST- 2016/09/07 06:00 [medline]
PHST- 2015/10/28 00:00 [pmc-release]
AID - ijn-10-6689 [pii]
AID - 10.2147/IJN.S90587 [doi]
PST - epublish
SO  - Int J Nanomedicine. 2015 Oct 28;10:6689-98. doi: 10.2147/IJN.S90587. eCollection 
      2015.