CYTOTOXICITY OF DEXTRAN-POLYACRYLAMIDE/GOLD NANOPARTICLES SYSTEMS AGAINST HUMAN EPIDERMAL CARCINOMA CELL LINES

Background. Modern achievements in polymer chemistry, medicine and biology have created the necessary basis for the search of complex delivery systems for anticancer compounds. Polymeric nanocarriers are promising drug delivery systems due to their unique physicochemical properties. Additional functionalization of the systems is provided by the addition of active components, such as small organic molecules, metal nanoparticles, other polymers, etc. However, despite a number of advantages, the clinical application of such systems is limited due to insufficient information on the behavior and effect on cells. Methods. The nanosystems dextran-graft-polyacrylamide (D500PAA)/gold nanoparticles (AuNPs) and dextran-graft-(co-polyacrylamide-co-polyacrylic acid) (D500PAAac)/AuNPs were used. The study was carried out on human laryngeal epidermal carcinoma (Hep-2), oral epidermal carcinoma (KB) and non-malignant mouse aortic endothelial cells (MAEC). The activities of lactate dehydrogenase (LDH), succinate dehydrogenase (SDH), glucose-6-phosphate dehydrogenase (G6PD) and the level of intracellular ROS were determined. Results. Nanosystems D500PAA/AuNPs showed higher cytotoxicity compared to D500PAAac/AuNPs. The detected changes in G6PD activity in Hep2-2 and KB cells have the opposite direction, which is probably a sign of adaptation of KB cells to the presence of polymeric nanocarriers and AuNPs. In KB cells, an increase in LDH activity was detected after incubation with D500PAAac and D500PAAac/AuNPs. D500PAA showed higher cytotoxicity and a stronger effect on the activity of the studied enzymes compared to anionic D500PAAac. More significant changes in LDH were detected in malignant cells, while SDH activity for them changes weakly. At the same time, the differences in SDH activity are most significant in MAES cells. ROS levels in cancer cells changed slightly, while in MAEC cells a 1.3-fold decrease was observed upon incubation with D500PAAac/AuNPs and a 3.5-fold decrease with D500PAA/AuNPs. Conclusions. The neutral polymer nanocarrier D500PAA has higher cytotoxicity compared to the anionic analogue D500PAAac against malignant Hep-2, KB and non-malignant MAEC cell lines. AuNPs encapsulated in the indicated polymer matrices exhibit weaker cytotoxicity in combination with D500PAAac, as well as changes in the activities of lactate dehydrogenase, succinate dehydrogenase and glucose-6-phosphate dehydrogenase and the effect on the level of intracellular ROS.