TIME-DEPENDENT MODULATION OF REACTIVE OXYGEN SPECIES IN LYMPHOMA CELLS BY A THIAZOLE DERIVATIVE AND ITS COMPLEX WITH A POLYMERIC NANOCARRIER

Abstract

Background. Thiazole-based molecules are promising anticancer candidates that disrupt the redox balance of tumor cells, but the impact of polymer carriers on their acti­vity remains poorly understood. This study evaluated how a 2-amino-5-benzylthiazole derivative (BF1) and its complex with a PEG-based polymer (Th4) influence reactive oxygen species (ROS) generation in Nemeth–Kellner lymphoma (NK/Ly) cells, using the free polymer (Th3) as a control.
Materials and Methods. NK/Ly lymphoma cells obtained from ascitic tumors in mice were incubated with BF1, the free polymer carrier Th3, or the BF1–polymer comp­lex Th4 at equal concentrations. After 30, 60, and 120 minutes of incubation, intracellular ROS levels were evaluated by fluorescence microscopy using a ROS-sensitive probe, and fluorescence intensity was quantified with image analysis software. Group differences were assessed by standard statistical tests, and correlation analysis was applied to examine the relationship between incubation time and ROS levels.
Results. Treatment with BF1 led to a significant, time-dependent increase in intracellular ROS compared with untreated control cells, indicating that this thiazole derivative effectively enhances oxidative stress in lymphoma cells. The free polymer Th3 did not cause meaningful changes in ROS at any time point, supporting its role as an inert carrier. In contrast, cells exposed to the BF1–polymer complex Th4 consistently showed a more pronounced elevation of ROS than those treated with BF1 alone at all incubation times. Correlation analysis revealed a moderate positive association between incubation time and ROS levels for BF1, and a stronger positive association for Th4, suggesting that polymer complexation intensifies and prolongs ROS accumulation in tumor cells.
Conclusions. A 2-amino-5-benzylthiazole derivative markedly increases ROS levels in lymphoma cells, an effect further amplified by its polymer complexation without additional toxicity from the free carrier. These findings indicate that induction of oxidative stress is a key mechanism of the derivative’s antitumor action. The inert nature of the free polymer confirms its suitability as a nanocarrier, while the enhanced ROS gene­ration supports further development of polymer-based thiazole formulations for cancer therapy.