RESUMEN
BACKGROUND: Breast cancer is one of the most common type of female cancer worldwide and represents 14% of cancer-related deaths in women. Early detection is the most important factor for treatment and prognosis of breast cancer. In most countries, the women are currently screened with mammography only. Even though there has been considerable progress in the detection, surgical therapy, hormonal and target therapy of breast cancer, there are about ⼠3500 000 women who die from breast cancer each year. Therefore, there is an urgent need to explore the new techniques for early detection of breast cancer. Magnetic resonance imaging (MRI) has the potential to improve breast cancer detection at an early stage because of its higher sensitivity. Glucose transporter (Glut) is a cellular transmembrane receptor that plays key roles in cell glucose metabolism and over-expressed in breast cancer cells. 2-deoxy-D-glucose having a similar structure to D-glucose can specifically interact with Glut. METHODS: In the present study, we constructed a 2-deoxy-D-glucose-functionalized superparamagnetic iron oxide (SPIO) nanoparticles that coated with meso-2,3-dimercaptosuccinic acid (γ-Fe2O3@DMSA-DG NPs). The aim of this study is to evaluate the efficacy of new constructed MRI contrast agent (γ-Fe2O3@DMSA-DG NPs) in detecting human breast cancers. RESULTS: Our results showed that breast cancer cells MDA-MD-231, MCF7 and ZR-75-1 had a high uptake rate of γ-Fe2O3@DMSA-DG NPs than human breast fibroblast cell HUM-CELL-0056. There was a significant difference of T2 relaxation times and signal intensity between breast cancer cells and human breast fibroblast cells labeled with γ-Fe2O3@DMSA-DG NPs when MIR. CONCLUSION: Our results indicated that γ-Fe2O3@DMSA-DG NPs may be used as a new MRI contrast agent for detection of breast cancer.
Asunto(s)
Neoplasias de la Mama/diagnóstico , Rastreo Celular/métodos , Detección Precoz del Cáncer , Nanopartículas de Magnetita/administración & dosificación , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Desoxiglucosa/administración & dosificación , Desoxiglucosa/química , Femenino , Compuestos Férricos/administración & dosificación , Compuestos Férricos/química , Fibroblastos/metabolismo , Humanos , Células MCF-7 , Imagen por Resonancia Magnética , Nanopartículas de Magnetita/química , Succímero/químicaRESUMEN
PURPOSE: This study aims to evaluate the effect of dimercaptosuccinic acid (DMSA)-coated superparamagnetic iron oxide (γ-Fe(2)O(3)@DMSA) bearing the 2-deoxy-D-glucose (2-DG) ligand on targeting tumors with high-glucose metabolism. PROCEDURES: γ-Fe(2)O(3)@DMSA and 2-DG-conjugated γ-Fe(2)O(3)@DMSA (γ-Fe(2)O(3)@DMSA-DG) were prepared. The glucose consumption of MDA-MB-231 and MCF-7 breast cancer cells and human mammary epithelial cells (HMEpiCs) was assessed. Cells were incubated with γ-Fe(2)O(3)@DMSA or γ-Fe(2)O(3)@DMSA-DG, and MDA-MB-231 cells which exhibited the highest glucose consumption were used in breast cancer xenografts. Tumor targeting was studied by magnetic resonance imaging and Prussian blue staining in vivo. RESULTS: Glucose consumption was highest in MDA-MB-231 and lowest in HMEpiCs. In vitro, there was significant uptake of γ-Fe(2)O(3)@DMSA-DG by MDA-MB-231 and MCF-7 cells within 2 h and this was inhibited by glucose. Uptake of γ-Fe(2)O(3)@DMSA-DG was significantly higher in MDA-MB-231 compared with MCF-7 cells, and there was no obvious uptake of γ-Fe(2)O(3)@DMSA in either cell line. In vivo, γ-Fe(2)O(3)@DMSA-DG could be detected in the liver and in tumors post-injection, while γ-Fe(2)O(3)@DMSA was nearly undetectable in tumors. CONCLUSIONS: 2-DG-coated γ-Fe(2)O(3)@DMSA improved tumor targeting of γ-Fe(2)O(3)@DMSA which can be assessed by magnetic resonance imaging.