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

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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.

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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

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Acknowledgements

Supported by PBRC/LSU, Nutrition and Chronic Disease Section, pilot project award: Detection of disseminated cells and micrometastases by ligand conjugated superparamagnetic iron oxid nanoparticles. PI: Carola Leuschner.

Financial support from the Center of Advanced Microstructures and Devices is gratefully acknowledged. The authors thank Dr Yuri Lvov and his team from the Louisiana Tech University, Ruston for providing the measurements for the zeta potentials.

Part of this study was published as a communication (Carola Leuschner, Challa SSR Kumar, Josef Hormes, William Hansel. Targeting breast cancer cells and their metastases through luteinizing hormone releasing hormone (LHRH) receptors using magnetic nanoparticles. Journal of Biomedical Nanotechnology Vol 2, 229–233, 2005.)

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Authors and Affiliations

  1. Pennington Biomedical Research Center, LSU System, Baton Rouge, LA, USA

    Carola Leuschner & William Hansel

  2. Center for Advanced Microsystems and Devices, Louisiana State University, Baton Rouge, LA, USA

    Challa SSR Kumar & Josef Hormes

  3. Princeton University, Princeton, NJ, USA

    Wole Soboyejo

  4. Lawrence Livermore National Laboratory, Livermore, CA, USA

    Jikou Zhou

  5. Reproductive Biotechnology, Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA, 70808, USA

    Carola Leuschner

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  1. Carola Leuschner
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  2. Challa SSR Kumar
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Correspondence to Carola Leuschner.

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Leuschner, C., Kumar, C.S., Hansel, W. et al. LHRH-conjugated Magnetic Iron Oxide Nanoparticles for Detection of Breast Cancer Metastases. Breast Cancer Res Treat 99, 163–176 (2006). https://doi.org/10.1007/s10549-006-9199-7

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