Document Detail


LHRH-conjugated magnetic iron oxide nanoparticles for detection of breast cancer metastases.
MedLine Citation:
PMID:  16752077     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Targeted delivery of superparamagnetic iron oxide nanoparticles (SPIONs) could facilitate their accumulation in metastatic cancer cells in peripheral tissues, lymph nodes and bones and enhance the sensitivity of magnetic resonance imaging (MRI). The specificities of luteinizing hormone releasing hormone (LHRH) and luteinizing hormone/chorionic gonadotropin (LH/CG)- bound SPIONs were tested in human breast cancer cells in vitro and were found to be dependent on the receptor expression of the target cells, the time of incubation and showed saturation kinetics. In incubations with MDA-MB-435S.luc cells, the highest iron accumulation was 452.6 pg Fe/cell with LHRH-SPIONs, 203.6 pg Fe/cell with beta-CG-SPIONs and 51.3 pg Fe/cell with SPIONs. Incubations at 4 degrees C resulted in 1.1 pg Fe/cell. Co-incubation with the same ligands (betaCG or LHRH) decreased the iron accumulation in each case. LHRH-SPIONs were poorly incorporated by macrophages. Tumors and metastatic cells from breast cancer xenografts were targeted in vivo in a nude mouse model. LHRH-SPION specifically accumulated in cells of human breast cancer xenografts. The amount of LHRH-SPION in the lungs was directly dependent on the number of metastatic cells and amounted to 77.8 pg Fe/metastastic cell. In contrast, unconjugated SPIONs accumulated in the liver, showed poor affinity to the tumor, and were not detectable in metastatic lesions in the lungs. LHRH-SPION accumulated in the cytosolic compartment of the target cells and formed clusters. LHRH-SPIONs did not accumulate in livers of normal mice. In conclusion, LHRH conjugated SPIONs may serve as a contrast agent for MR imaging in vivo and increase the sensitivity for the detection of metastases and disseminated cells in lymph nodes, bones and peripheral organs.
Authors:
Carola Leuschner; Challa S S R Kumar; William Hansel; Wole Soboyejo; Jikou Zhou; Josef Hormes
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-06-03
Journal Detail:
Title:  Breast cancer research and treatment     Volume:  99     ISSN:  0167-6806     ISO Abbreviation:  Breast Cancer Res. Treat.     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-08-23     Completed Date:  2007-04-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8111104     Medline TA:  Breast Cancer Res Treat     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  163-76     Citation Subset:  IM    
Affiliation:
Pennington Biomedical Research Center, LSU System, Baton Rouge, LA 70808, USA. Leuschc@pbrc.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Breast Neoplasms / metabolism,  pathology*
CHO Cells / metabolism
Carrier Proteins / metabolism*
Chorionic Gonadotropin, beta Subunit, Human / pharmacology
Contrast Media
Cricetinae
Cricetulus
Disease Models, Animal
Female
Ferrosoferric Oxide / metabolism*
Gonadotropin-Releasing Hormone / metabolism*
Humans
Lung Neoplasms / metabolism,  secondary*
Lymph Nodes / metabolism,  pathology
Lymphatic Metastasis / diagnosis
Macrophages / metabolism
Magnetic Resonance Imaging
Male
Mice
Mice, Nude
Nanoparticles
Receptors, LHRH / metabolism
Sensitivity and Specificity
Sertoli Cells / metabolism
Tissue Distribution
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Chorionic Gonadotropin, beta Subunit, Human; 0/Contrast Media; 0/Receptors, LHRH; 1317-61-9/Ferrosoferric Oxide; 33515-09-2/Gonadotropin-Releasing Hormone

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