Introduction: Titanium dioxide (TiO2) nanoparticles with their unique physicochemical properties have found widespread applications in biomedical fields. However, investigations have been performed regarding their potential cytotoxic effects, particularly in malignancies such as acute lymphoblastic leukemia. This study aimed to evaluate the cytotoxicity of TiO₂ nanoparticles and their correlation with the expression of the SYNGAP1 gene, a gene involved in cellular signaling and survival in MOLT-4 leukemia cell lines. Material and Method: In this experimental study, MOLT-4 cell lines were divided into 2 groups: 1) control group, 2) TiO₂ group (exposed to a variety of TiO₂ nanoparticle concentrations (0.2, 0.4, 0.6, 0.8, 1 μg/ml). Cytotoxic effects were assessed using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and flow cytometry. In addition, the Gene expression analysis was performed using Real-time PCR to quantify SYNGAP1 mRNA levels. Data were analyzed using GraphPad Prism version 8. One-way analysis of variance (ANOVA) was used to assess differences between groups, and p<0.05 was considered significant. Results: The results demonstrated that TiO₂ nanoparticles induced a dose- and time-dependent cytotoxicity in the MOLT-4 cells. Furthermore, SYNGAP1 gene expression was significantly (p< 0.05) down-regulated in the treated cells compared to the control group. Conclusion: These findings suggest that TiO₂ nanoparticles possess potential anti-cancer properties by inhibiting the proliferation of MOLT-4 cells, possibly through downregulation of SYNGAP1 Gene. Suppression of this gene may disrupt cellular functions and contribute to the apoptosis of these cancerous cells.
