Magnetic Fe3O4 nanoparticles and chemotherapy agents interact synergistically to induce apoptosis in lymphoma cells

Abstract

Hongmei Jing1, Jing Wang1, Ping Yang1, Xiaoyan Ke1, Guohua Xia2, Baoan Chen21Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing, People’s Republic of China; 2Department of Hematology, The Affiliated Zhongda Hospital, Clinical Medical School, Southeast University, Nanjing, People’s Republic of ChinaAbstract: The purpose of this study was to investigate the potential effects of combination therapy using magnetic nanoparticles of Fe3O4 (MNP-Fe3O4) and chemotherapeutic drugs on lymphoma cells. Proliferation, inhibition, and viability of Raji cells were detected by MTT and trypan blue exclusion. The percentage of cells undergoing apoptosis was detected by flow cytometry using fluorescein isothiocyanate-annexin V and propidium iodide staining. p53 and nuclear factor-κB (NF-κB) protein levels were measured by Western blot. The results showed that proliferation of Raji cells was inhibited by adriamycin or daunorubicin in a dose-and time-dependent manner. Cell sensitivity was improved and the 50% inhibitory concentrations of adriamycin and daunorubicin decreased when combined with a MNP-Fe3O4 carrier. Interestingly, increased apoptosis in Raji lymphoma cells was accompanied by upregulation of p53 protein and downregulation of NF-κB protein. Furthermore, the combination of MNP-Fe3O4 with adriamycin or daunorubicin increased p53 protein levels and decreased NF-κB protein levels more than adriamycin or daunorubicin alone, indicating that MNP-Fe3O4 could enhance the effect of chemotherapeutic drugs on p53 and NF-κB. Similar results for cell apoptosis and protein expression were not observed for the groups treated with dexamethasone ± MNP-Fe3O4 (P >0.05). These findings suggest a potential clinical application for MNP-Fe3O4 in combination with daunorubicin or adriamycin in the treatment of lymphoma.Keywords: magnetic nanoparticles, Raji cells, apoptosis, p53, NF-κB