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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.

Surface biofunctionalization of the hydrophobic lanthanide ion doped hexagonal phase NaYF4:Yb,Er upconversion nanophosphors (UCNPs) was achieved by introducing amino and carboxyl groups, respectively. Amino groups were added by using the 3-aminopropyltrimethoxysilane reaction after a thin layer of SiO2 coating. The carboxyl groups on surface were added directly by coating modified amphiphilic polyacrylic acid polymer. Experimental studies of cytotoxicity and cell uptake of UCNPs were conducted. The cytotoxicity analysis of the functionalized UCNPs was conducted by methylthiazol tetrazolium assays. Cell uptake was accomplished by incubating the UCNPs with human osteosarcoma cells and proved by transmission electron microscopy. The results showed that the functionalized UCNPs had very low toxicity compared with the control group, while UCNPs taken into the cells indicated that they had very high biocompatibility. The imaging of UCNPs, which were incubated with AB12 mouse mesothelioma cells and excited by 1 W 980 nm light, showed individual particles with visible light emission. These results exhibited promising applications of functionalized UCNPs in cell imaging and photodynamic therapy.

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