Effect of magnetic fluid hyperthermia with dendrimer coated iron oxide nanoparticles on breast cancer in BALB/c mice

Abstract

Introduction: Magnetic fluid hyperthermia (MFH) is a promising therapeutic method in cancer therapy with using magnetic nanoparticles (NPs). In this study, we assessed the effect of MFH on mechanisms of cell death in murine breast cancer cell line (MC4-L2) and also the treatment of breast tumor in BALB/C mice using four generation dendrimer coated iron oxide nanoparticles (G4@IONPs). Materials and Methods: Immediately after MFH, the viability of cells was assessed in all groups (MFH+NPs, only MFH, only NPs, control) by MTT assay. In order to determine the number of apoptosis and mRNA copies for Bax and Bcl-2 in the cells after MFH, TUNEL assay and RT-PCR were performed, respectively. The mice were exposed three times during twenty minutes to an MFH (12 kA/m, 300 kHz) after intertumoral injection of 5mg G4@IONPs. The temperature during MFH was monitored with an infrared thermometer (FLIR Systems). Tumor volume was measured during 28 days after MFH. Histopathology, Immunohistochemical staining, and TUNEL assay were performed in the liver and tumor tissues. Results: Cell viability percentage in the group of MFH+NPs decreased significantly (33%, P<0.05) while the viability in other groups had no any significant change. Also, the number of apoptotic cells and Bax/Bcl-2 ratio in MFH+NPs increased significantly. The MFH led to significantly reduce the volume of the tumor 30 days after the treatment compared with control mice (saline injection) (p < 0.05). tissue destruction obviously was seen in tumor histopathology of MFH+NPs mice. CD31 as angiogenesis marker decreased in treated tumors compared with control ones and furthermore, apoptosis significantly increased in treated tumor tissues. Conclusion: Our study showed MFH with G4@IONPs could demolish the cancer cells mainly because of increasing the apoptosis and regulating the apoptotic genomes including Bax and Bcl-2. MFH can applied as a clinical anti-cancer strategy due to inhibition of tumor angiogenesis.