Antitumor Efficacy of DMSA Modified Fe₃O₄ Magnetic Nanoparticles Combined with Arsenic Trioxide and Adriamycin in Raji Cells

Abstract

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 (Raji cells). The growth inhibition rate of Raji cells was determined by MTT assay. Characteristics of DMSA-Fe3O4 MNPs and distribution of nanoparticles taken up by Raji 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, NFKB, 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 Raji 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 Raji cells from ADM-As,O3 MNPs group clearly exhibited more morphological changes (severe structural alterations) than other groups. Moreover, transcription and protein expression of bcl-2, NFKB, survivin, bax, p53 and caspase-3 of Raji 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 Raji cells would be a promising strategy for lymphoma therapy.

Inducing cell cycle arrest and apoptosis by dimercaptosuccinic acid modified Fe3O4 magnetic nanoparticles combined with nontoxic concentration of bortezomib and gambogic acid in RPMI-8226 cells

“…25 Average hydrodynamic size of aggregates of DMSA-Fe 3 O 4 dispersed in Roswell Park Memorial Institute (RPMI) 1640 medium (Gibco, USA) containing 10% (v/v) inactivated fetal calf serum (Sijiqing Biological Engineering Materials Co., Ltd., Hangzhou, People's Republic of China) is 68.4 nm. 26 BTZ was obtained from Janssen-Cilag (Neuss, Germany).…”

Size-dependent cytotoxicity of Fe₃O₄ nanoparticles induced by biphasic regulation of oxidative stress in different human hepatoma cells

“…The cellular membrane damage assay was performed using the LDH Cytotoxicity Assay Kit that can quantitatively evaluate the degree of cellular membrane damage associated with the leakage of the cytosolic LDH. SK-Hep-1 and Hep3B cells (2×10 4…”

“…Magnetic iron oxide (Fe 3 O 4 ) nanoparticles (NPs) have been applied in a wide range of biomedical and medical areas, including cell labeling, 1,2 separation and tracking, 3 drug delivery, 4 diagnosis, 5 and hyperthermia for cancer therapy. 6 Due to the unique properties of Fe 3 O 4 NPs, much progress in the development of its application has been made.…”

Biocompatible superparamagnetic nanoparticles with ibuprofen as potential drug carriers

“…Since these nanoparticles present superparamagnetic behavior, they can be guided to target sites by applying an external magnetic field, which allows the control over their biodistribution [12,13]. In addition, these nanoparticles are much less toxic than their correlative materials [14][15][16].…”