LHRH-conjugated magnetic iron oxide nanoparticles for detection of breast cancer metastases

• Published in: Breast cancer research and treatment Vol. 99; no. 2; pp. 163 - 176
• Main Authors: LEUSCHNER, Carola, KUMAR, Challa S. S. R, HANSEL, William, SOBOYEJO, Wole, JIKOU ZHOU, HORMES, Josef
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer 01.09.2006; Springer Nature B.V
• Subjects: Animals; Biological and medical sciences; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer research; Cancer therapies; Carrier Proteins - metabolism; CHO Cells - metabolism; Chorionic Gonadotropin, beta Subunit, Human - pharmacology; Contrast Media; Cricetinae; Cricetulus; Disease Models, Animal; Female; Ferrosoferric Oxide - metabolism; Gonadotropin-Releasing Hormone - metabolism; Gynecology. Andrology. Obstetrics; Hormones; Humans; Iron; Lung Neoplasms - metabolism; Lung Neoplasms - secondary; Lymph Nodes - metabolism; Lymph Nodes - pathology; Lymphatic Metastasis - diagnosis; Macrophages - metabolism; Magnetic Resonance Imaging; Male; Mammary gland diseases; Medical research; Medical sciences; Mice; Mice, Nude; Nanoparticles; NMR; Nuclear magnetic resonance; Receptors, LHRH - metabolism; Sensitivity and Specificity; Sertoli Cells - metabolism; Tissue Distribution; Tumor Cells, Cultured; Tumors; Nanoparticle; Gonadotropin RH; Iron; Breast cancer; Malignant tumor; Metastasis; Hypothalamic hormone; Mammary gland diseases; Protein hormone; metastases; Magnetic; luteinizing hormone releasing hormone receptors; nanoparticles; Adenohypophyseal hormone; superparamagnetic iron oxide nanoparticles; Luteinizing hormone; Microparticle; Chorionic gonadotrophin; Diagnosis; Hormone releasing factor; Detection; Biological receptor; Hormonal receptor; chorionic gonadotropin receptors
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-006-9199-7

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.