Antitumor Efficacy Of DMSA Modified Fe₃O₄ magnetic Nanoparticles Combined With Arsenic Trioxide and Adriamycin In Jurket Cells

The objective of the present study was to investigate the anticancer efficacy of dimercaptosuccinic acid modified iron oxide (DMSA-Fe₃O₄) magnetic nanoparticles (MNPs) combined with arsenic trioxide (As₂O₃) and doxorubicin (ADM) in non-Hodgkin's lymphoma (NHL) cell line (Jurket cells). The growth inhibition rate of Jurket cells was determined by MTT assay. Characteristics of DMSA-Fe₃O₄MNPs and distribution of nanoparticles taken up by Jurket cells were observed under a transmission electron microscopy (TEM). Further, apoptosis of cells and intracellular concentration of ADM were detected by flow cytometry (FCM). DAPI staining was used to view apoptotic cellular morphology. Subsequently, transcription and protein expression levels of bcl-2, NF¦ÊB, survivin, bax, p53 and caspase-3 were determined by reverse transciptase polymerase chain reaction (RT-PCR) and Western blotting analysis, respectively. The results of MTT assay indicated that the inhibition of Jurket cells by the combined form of ADM and As₂O₃ was significantly higher than either ADM or As₂O₃ alone. However, ADM-As₂O₃ MNPs proved superior over all other groups. TEM observation revealed that the majority of MNPs were quasi-spherical with an average diameter of about 18 nm and the MNPs taken up by cells were located in the endosome vesicles of cytoplasm. The apoptotic rate and accumulation of intracellular ADM in ADM-As₂O₃ MNPs group were significantly higher than those in control, ADM, As₂O₃ and ADM + As₂O₃ groups. In addition, DAPI staining of Jurket cells from ADM-As₂O₃ MNPs group clearly exhibited more morphological changes (severe structural alterations) than other groups. Moreover, transcription and protein expression of bcl-2, NF¦ÊB, survivin, bax, p53 and caspase-3 of Jurket cells were regulated at the most remarkable extent in ADM-As₂O₃ MNPs group as compared with other groups. These findings suggest that the antitumor efficacy of the combination of novel ADM-As₂O₃ MNPs on Jurket cells would be a promising strategy for lymphoma therapy.