Zinc Oxide Nanoparticles Functionalized with Ascorbic Acid and Conjugated with Chitosan Change Apoptotic Gene...

Gastric cancer poses a significant global health challenge, with current treatment options like chemotherapy often resulting in toxicity to healthy cells. In this context, nanomedicine emerges as a promising strategy to enhance drug delivery and minimize adverse effects. This study focuses on developing Zinc oxide nanoparticles (ZnO-NPs) that are functionalized with ascorbic acid and conjugated with chitosan (ZnO@AsA/CS) to improve their efficacy and cellular uptake for targeting gastric adenocarcinoma cells (AGS). The ZnO-NPs were synthesized and modified to form ZnO@AsA/CS. Various characterization techniques, including X-ray diffraction (XRD), dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FTIR), polydispersity index (PDI), scanning electron microscopy (SEM), and transmission electron microscopy (TEM), were utilized to assess their properties. The cytotoxic effects of the nanoparticles for AGS and HGF-1 normal cells were evaluated through MTT assays. For AGS cells, lactate dehydrogenase (LDH) assays were conducted to examine cell membrane integrity. Additionally, the activity of Caspase-3, Caspase-8, and Caspase-9 was analyzed to explore apoptotic pathways. The generation of reactive oxygen species was measured using DCFH-DA staining, and the expression of apoptotic markers was analyzed via quantitative reverse transcription polymerase chain reaction (qRT-PCR). The characterization process revealed that the ZnO@AsA/CS nanoparticles had a uniform size distribution, averaging between 100 to 200 nm. MTT assay results indicated a dose-dependent reduction in AGS cell viability, with an IC₅₀ of 78.4µg/ml. LDH assays confirmed the cytotoxicity profile consistent with the MTT results. Following treatment with ZnO@AsA/CS, significant changes in the expression of apoptotic genes were noted, including downregulation of Bcl-2 and upregulation of Caspase-3 and Caspase-8 and Caspase-9. Overall, the study suggests that ZnO@AsA/CS could serve as an effective therapeutic strategy for treating gastric adenocarcinoma.