Sodium hexametaphosphate-induced enhancement of silver nanoparticle toxicity towards leukemia cells

Synergistic effects occurring between biologically active substances are of great importance for efficient treatment of many diseases. Therefore, the aim of research was to determine impact of sodium hexametaphosphate (HEX), which is a well-known permeabilizer, on the cytotoxicity of silver ions and two types of AgNPs towards HL-60 and U-937 tumor cells. The AgNPs were synthesized in a chemical reduction method using sodium borohydride and trisodium citrate (CITAgNPS) or sodium hypophosphite and HEX (HEXAgNPs). Imaging with the use of transmission electron microscopy (TEM) and atomic force microscopy (AFM) revealed that the AgNPs exhibited spherical shape and comparable size distribution. Electrophoretic mobility studies showed that the AgNPs were negatively charged. The mitochondrial and antioxidant activity as well as membrane lipid peroxidation and integrity after dose-dependent AgNP treatment were evaluated using biochemical assays. The impact of HEXAgNPs on the membrane integrity and inactivation of antioxidant enzymes of the cells was much higher than this one observed for CITAgNPs and silver ions of the same concentration. The membrane damage occurred as a result of lipid peroxidation which was induced by pure HEX and HEXAgNPs. It was also observed that HEX significantly increased cell membrane damage induced by CITAgNPs and silver ions although the cells exhibited different sensitivity to these components. Moreover, it was found that HEX can induce oxidative stress. Hence, it was revealed that HEX enhances AgNP activity when it is applied both as their stabilizer or supplement in their suspensions.