Breast Cancer Research and Treatment

, Volume 99, Issue 2, pp 163–176

LHRH-conjugated Magnetic Iron Oxide Nanoparticles for Detection of Breast Cancer Metastases

Authors

    • Pennington Biomedical Research CenterLSU System
    • Reproductive BiotechnologyPennington Biomedical Research Center
  • Challa SSR Kumar
    • Center for Advanced Microsystems and DevicesLouisiana State University
  • William Hansel
    • Pennington Biomedical Research CenterLSU System
  • Wole Soboyejo
    • Princeton University
  • Jikou Zhou
    • Lawrence Livermore National Laboratory
  • Josef Hormes
    • Center for Advanced Microsystems and DevicesLouisiana State University
Preclinical study

DOI: 10.1007/s10549-006-9199-7

Cite this article as:
Leuschner, C., Kumar, C.S., Hansel, W. et al. Breast Cancer Res Treat (2006) 99: 163. doi:10.1007/s10549-006-9199-7

Summary

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 β-CG-SPIONs and 51.3 pg Fe/cell with SPIONs. Incubations at 4 °C resulted in 1.1 pg Fe/cell. Co-incubation with the same ligands (βCG 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.

Key words

breast cancer chorionic gonadotropin receptors luteinizing hormone releasing hormone receptors metastases nanoparticles superparamagnetic iron oxide nanoparticles

Abbreviations

LHRH

luteinizing hormone releasing hormone

CG

chorionic gonadotropin

βCG

fragment of the beta chain of CG from amino acid 81–95

MRI

magnetic resonance imaging

SPION

superparamagnetic iron oxide nanoparticles

CT

computed tomography

PET

positron emission tomography

CHO

Chinese Hamster Ovary Cells

PMA

4α Porbol 12 myristate 13 acetate

s.c.

subcutanously

Copyright information

© Springer 2006