Effect of thiazole derivative complexed with nanoscale polymeric carriers on cellular ultrastructure of murine lymphoma cells in vivo

Abstract

Background. A pronounced cytotoxic action of the thiazole derivatives complexed with polymeric carriers on tumor cells in vitro was reported earlier, while no cytotoxicity of these compounds was detected toward noncancerous cells. It was found that thiazole derivatives at concentrations of 10 and 50 µM affected lymphoma cell ultrastructure in vitro. The purpose of this work was to investigate the effect of thiazole derivative 8-methyl-2-Me-7-[trifluoromethyl-phenylmethyl]-pyrazolo-[4,3-e]-[1,3]- thiazolo-[3,2-a]-pyrimidin-4(2H)-one (PP2) and its complexes with polymeric carriers poly(VEP-co-GMA)-graft-mPEG (Th12) and poly(PEGMA) (Th14) on the ultrastructure of lymphoma cells in vivo. Materials and Methods. Experiments were conducted on white wild-type male mice with grafted NK/Ly lymphoma. Ascite tumors were created by intreperitoneal inocu­lation of 1–2 mln of Nemet–Kelner lymphoma cells to mice. On the 12th day after inoculation, the body weight of animals was increased by 140–160 % mostly due to ascites growth. For treatment of ascites three solutions of the chemical compounds were prepared: PP2, PP2 + Th12, PP2 + Th14 and administered to the mice intraperitoneally for 5 days. The final concentration of PP2 was 5 mg/kg of body weight. Abdominal drainage from ascites was performed with a sterile syringe under chloroform anesthesia on the 10th day after the start of treatment. The ultrastructure of the cells was examined by electron microscopy. Results. Еlectron microscopy study showed that control lymphoma cells have a special subcellular formations such as a relatively large nucleus, and specific plasma membrane filaments. The effects of thiazole derivative revealed apoptotic and necrotic manifestations of cytotoxicity, such as a deformation and disintegration of nucleus, a decreased nucleus/cytoplasm ratio, a destruction of the plasma membrane and a change of mitochondria shape. The studied compound complexed with polymeric carriers caused an apoptotic-like changes in lymphoma cells. Under the action of such complexes, the nucleus/cytoplasm ratio decreased and the area of mitochondria increased. Conclusions. The obtained results suggest that the tested compounds induce apoptosis in tumor cells. Complexes of thiazole derivative with polymers do not impair the effect of the compound on lymphoma cells. The obtained data can be used to carry out further preclinical studies of thiazole derivatives complexed with polymeric carriers as potential antitumor drugs.

Analysis of survival and morphometric parameters of loach embryos and prelarvae under the action of the polyethyleneglycol derivative polymeric nanocarrier

“…As is known, polymeric carriers improve the delivery of chemical compounds to the cell. Earlier, it was shown that a 2-amino-5-benzylthiazole derivative in a complex with a PEG-containing carrier (Popovych et al, 2021) did not impair the effect of antineoplastic compounds on lymphoma cells, but caused the lymphoma cells death through apoptotic changes. As C. Yang, H.-Z.…”

Generation of ROS under the influence of thiazole derivative and its complexes with PEG-based polymeric nanoparticles

“…PEG-based polymeric nanoparticles (PEG-PNs) may conjugate with many therapeutic anticancer agents increasing solubility and blood-circulation time of antitumor che mi cals, improving targeted delivery to tumor tissues, decreasing side effects on healthy cells, and, as a result, these nanoparticles improve the efficacy of drugs [5,6]. It was established, that combination of BF1 with the polymeric carriers based on polyethylene glycol (PEG) increases the cytotoxicity towards several tumor cell lines [7], causing the apoptotic-like alterations in the mice Nemeth-Kellner lymphoma (NK/Ly) cells [8] and increasing the level of superoxide dismutase (SOD), one of the most important enzyme of the antioxidant defense system [9].…”