Disulfiram-loaded functionalized magnetic nanoparticles combined with copper and sodium nitroprusside in breast cancer cells

Disulfiram (DSF), one of the members of the dithiocarbamate family, is a reactive species (RS) generator and is capable of inducing cancer cell death in breast cancer. However, it is hydrophobic and highly degradable in blood. Therefore, drug delivery systems would be of great benefit in supporting the selective accumulation of DSF in tumor cells. In this study, it was aimed to prepare a drug carrier system based on magnetic mesoporous silica nanoparticles (Fe3O4@mSiO(2) MNPs) which are non-toxic, biocompatible, and have a mesoporous structure. The Fe3O4@mSiO(2) MNPs were modified with folic acid linked polyethyleneimine (PEI-FA) to increase both their solubility in water and specificity for cancer cells. Thus, the cancer-selective DSF-carrier system (mMDPF) was synthesized with a high surface area but with dimensions of less than 160 nm, and were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM) and Brunauer-Emmett-Teller (BET) analysis. The drug-loading capacity of mMDPF was measured as 4.35% by high-performance liquid chromatography (HPLC) and the best drug release kinetics of mMDPF was observed at 37 degrees C and pH 6.0 which is the pH in the endosome. The cytotoxicity of the mMDPF on breast cancer (MCF-7) cells was improved by applying mMDPF with copper and/or sodium nitroprusside. It was observed that mMDPF was taken up more by MCF-7 cells and its toxicity on MCF-7 cells was much higher than non-tumorigenic (MCF-10A) cells.

Automated summary

Disulfiram, a reactive species generator, can induce cancer cell death in breast cancer but it degrades easily in blood. This study prepared a drug carrier system based on magnetic mesoporous silica nanoparticles to support selective accumulation of DSF in tumor cells. The system showed high drug-loading capacity and achieved cancer-selective accumulation through modifications with folic acid linked polyethyleneimine. The cytotoxicity of the system on breast cancer cells was higher than on non-tumorigenic cells due to enhanced uptake by cancer cells.